Epigenetics Podcast

Chromatin State Reprogramming in Cancer Progression (Kunal Rai)

In this episode of the Epigenetics Podcast, we talked with Kunal Rai from MD Anderson Cancer Center about his work on chromatin state reprogramming in cancer progression. A major part of the conversation covers his postdoctoral work on active DNA demethylation. He describes how he identified an AID-MBD4-based mechanism, later supported by GAD45, and how this work showed a role for DNA demethylation in early neuronal differentiation and in colon cancer initiation. We then discuss his move into his own lab and his work on melanoma progression. He explains how he used broad epigenomic profiling, chromatin state analysis, and 3D chromatin methods to study enhancers and chromatin organization, and how these approaches helped reveal changes linked to cancer progression. Another topic is his work on epigenetic regulators such as RNF2 and KMT2D. He describes findings on polycomb and trithorax-related factors, including tumor-suppressive roles for KMT2D in melanoma and lung cancer, and how KMT2D loss affects cell phenotype and metabolism. Finally, we talk about lab organization, collaboration, and newer technologies. He says his group works across multiple cancer types and increasingly includes immunology, single-cell methods, spatial epigenomics, and clinical translation, while still using ChIP-seq, CUT&RUN, and CUT&Tag where appropriate. References Fiziev, P., Akdemir, K. C., Miller, J. P., Keung, E. Z., Samant, N. S., Sharma, S., Natale, C. A., Terranova, C. J., Maitituoheti, M., Amin, S. B., Martinez-Ledesma, E., Dhamdhere, M., Axelrad, J. B., Shah, A., Cheng, C. S., Mahadeshwar, H., Seth, S., Barton, M. C., Protopopov, A., Tsai, K. Y., … Rai, K. (2017). Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression. Cell reports, 19(4), 875–889. https://doi.org/10.1016/j.celrep.2017.03.078 Terranova, C. J., Tang, M., Maitituoheti, M., Raman, A. T., Ghosh, A. K., Schulz, J., Amin, S. B., Orouji, E., Tomczak, K., Sarkar, S., Oba, J., Creasy, C., Wu, C. J., Khan, S., Lazcano, R., Wani, K., Singh, A., Barrodia, P., Zhao, D., Chen, K., … Rai, K. (2021). Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy. Cell reports, 36(3), 109410. https://doi.org/10.1016/j.celrep.2021.109410 Related Episodes Epigenetic Signatures During Aging and Cancer (Alena van Bömmel) Epigenetic Mechanisms in Breast Cancer (Luca Magnani) The Effect of Histone Demethylases on Gene Expression and Cancer Cell Stability (Johnathan Whetstine) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Statistical Physics Approaches to DNA Methylation and Aging (Steffen Rulands)

In this episode of the Epigenetics Podcast, we talked with Steffen Rulands from the Ludwig Maximilian University of Munich about how methods from statistical physics can be used to study collective phenomena in biology. We discuss his path from physics into stem cell biology and epigenetics, and how this background shapes the questions he asks in his work. We talk about his lab’s focus on quantitative and mechanistic modeling rather than wet lab experiments. He explains that he uses single-cell genomics and other datasets to understand how cells make decisions, with interests ranging from development and regeneration to aging and rejuvenation. A major topic is DNA methylation during embryonic development. We discuss how he and his collaborators found surprisingly simple, self-similar patterns in methylation over time and along the genome, and how they explained these patterns with a feedback loop between chromatin conformation and methylation deposition. We also cover his collaboration on social insect colonies, where he examines how DNA methylation and gene regulation help explain stable social roles and flexibility when the queen is removed. In that system, interactions across the whole nest shape the regulation of queen- and worker-associated genes. Later in the conversation, we turn to aging. We discuss his recent work on temporal hierarchies in epigenetic aging and on collective dynamics of DNA methylation, where we ask how molecular-scale events can combine to produce the long timescale of organismal aging. We close by talking about rejuvenation, general principles in aging, and the role of physics in identifying what is generic versus what is specifically regulated in biology. References Rulands, S., Lee, H. J., Clark, S. J., Angermueller, C., Smallwood, S. A., Krueger, F., Mohammed, H., Dean, W., Nichols, J., Rugg-Gunn, P., Kelsey, G., Stegle, O., Simons, B. D., & Reik, W. (2018). Genome-Scale Oscillations in DNA Methylation during Exit from Pluripotency. Cell systems, 7(1), 63–76.e12. https://doi.org/10.1016/j.cels.2018.06.012 Olmeda, F., Lohoff, T., Kafetzopoulos, I. et al. Scaling and self-similarity in the formation of the embryonic epigenome. Nat. Phys. 22, 931–940 (2026). https://doi.org/10.1038/s41567-026-03263-x Related Episodes Biophysical Modeling of 3-D Genome Organization (Leonid Mirny) The Interplay of Nutrition, Metabolic Pathways, and Epigenetic Regulation (Ferdinand von Meyenn) Epigenetic Reprogramming During Mammalian Development (Wolf Reik) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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From GAL4 to targeted DAM-ID: Tools for Studying Gene Expression In Vivo (Andrea Brand)

In this episode, we speak with Andrea Brand, Chair of the Department of Cell Biology at NYU Grossman School of Medicine and Director of the Regenerative Medicine Institute. We discuss her scientific path from yeast gene regulation to Drosophila neurobiology, and how early interests in DNA and microscopy shaped her career. We talk about the development of the GAL4 system with Norbert Perrimon and how it enabled targeted gene expression in specific tissues and cells. Andrea explains why this approach has remained useful across decades, including its applications in Drosophila and beyond, while noting that no experimental system is perfect and results should be cross-checked with other methods. We also discuss targeted DAM-ID and chromatin DAM-ID, methods developed in her lab to study protein-DNA interactions and chromatin marks in vivo without removing cells from their normal tissue environment. Andrea describes how these tools helped her lab analyze neural stem cells in their niche and investigate changes in chromatin during quiescence and reactivation. A major theme of the conversation is neural stem cell quiescence. We cover how her lab found that quiescent stem cells can show unexpectedly open chromatin, express neuronal genes, and adopt neuron-like features, including long projections and interactions with neurons. We also discuss the link to metabolism, including feeding signals, the fat body, blood-brain barrier glia, insulin-like peptides, and TGF-beta signaling. Finally, we talk about Andrea’s recent move toward human brain organoids and the goal of connecting model organism work to human biology and patient data. We discuss ongoing work on quiescent cells, TRIB family genes, and cancer–neuron interactions, as well as the need to better distinguish quiescence from senescence in vivo. References Brand, A. H., & Perrimon, N. (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development (Cambridge, England), 118(2), 401–415. https://doi.org/10.1242/dev.118.2.401 Southall, T. D., Gold, K. S., Egger, B., Davidson, C. M., Caygill, E. E., Marshall, O. J., & Brand, A. H. (2013). Cell-type-specific profiling of gene expression and chromatin binding without cell isolation: assaying RNA Pol II occupancy in neural stem cells. Developmental cell, 26(1), 101–112. https://doi.org/10.1016/j.devcel.2013.05.020 Tang, J. L. Y., Hakes, A. E., Krautz, R., Suzuki, T., Contreras, E. G., Fox, P. M., & Brand, A. H. (2022). NanoDam identifies Homeobrain (ARX) and Scarecrow (NKX2.1) as conserved temporal factors in the Drosophila central brain and visual system. Developmental cell, 57(9), 1193–1207.e7. https://doi.org/10.1016/j.devcel.2022.04.008 Cheetham, S. W., & Brand, A. H. (2018). RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites. Nature structural & molecular biology, 25(1), 109–114. https://doi.org/10.1038/s41594-017-0006-4 Cheetham, S. W., Gruhn, W. H., van den Ameele, J., Krautz, R., Southall, T. D., Kobayashi, T., Surani, M. A., & Brand, A. H. (2018). Targeted DamID reveals differential binding of mammalian pluripotency factors. Development (Cambridge, England), 145(20), dev170209. https://doi.org/10.1242/dev.170209 Related Episodes scDamID, EpiDamID and Lamina Associated Domains (Jop Kind) Characterizing Chromatin at the Nuclear Lamina (Bas van Steensel) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Antibodies, Automation, and the Fight for Reproducibility (Alon Goren)

In this episode we speak with Alon Goren from UC San Diego about his work at the intersection of genomic technology development and chromatin biology. We discuss how his lab studies how the epigenome is regulated, how disruption of that regulation contributes to disease, and how technology can be improved to make results more robust and reproducible. We talk about his early interest in biology, how that developed through medical research training, and how a molecular biology lab shaped the direction of his career. He explains how curiosity about how cells and organisms work led him toward genomics and chromatin research. We then discuss several methods from his career, including early direct sequencing approaches for small amounts of DNA and RNA, ChIP-based methods for chromatin regulators, and work on improving ChIP-seq workflows. He explains why antibody choice matters, why monoclonal antibodies can improve reproducibility, and how automation helped scale the process. We also cover his work on spike-in normalization, including the risks of using exogenous chromatin incorrectly and the need for better safeguards in genome-wide comparisons. He describes a newer approach that uses two spike-ins to provide multiple checks on normalization. Finally, we discuss his work on short tandem repeats, zebrafish heart regeneration, and SIRT6-related polymerase pausing, as well as a newer platform that converts molecular interactions into sequencing-readable barcodes. He closes by stressing the importance of validation, careful protocol design, and methods that can be used reliably by multiple people. References Ram, O., Goren, A., Amit, I., Shoresh, N., Yosef, N., Ernst, J., Kellis, M., Gymrek, M., Issner, R., Coyne, M., Durham, T., Zhang, X., Donaghey, J., Epstein, C. B., Regev, A., & Bernstein, B. E. (2011). Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells. Cell, 147(7), 1628–1639. https://doi.org/10.1016/j.cell.2011.09.057 Busby, M., Xue, C., Li, C., Farjoun, Y., Gienger, E., Yofe, I., Gladden, A., Epstein, C. B., Cornett, E. M., Rothbart, S. B., Nusbaum, C., & Goren, A. (2016). Systematic comparison of monoclonal versus polyclonal antibodies for mapping histone modifications by ChIP-seq. Epigenetics & chromatin, 9, 49. https://doi.org/10.1186/s13072-016-0100-6 Patel, L. A., Cao, Y., Mendenhall, E. M., Benner, C., & Goren, A. (2024). The Wild West of spike-in normalization. Nature biotechnology, 42(9), 1343–1349. https://doi.org/10.1038/s41587-024-02377-y Ben-Yair, R., Butty, V. L., Busby, M., Qiu, Y., Levine, S. S., Goren, A., Boyer, L. A., Burns, C. G., & Burns, C. E. (2019). H3K27me3-mediated silencing of structural genes is required for zebrafish heart regeneration. Development (Cambridge, England), 146(19), dev178632. https://doi.org/10.1242/dev.178632 Patel, L., Cao, Y., Xu, T., Modolo, E., Dishon, T., Zhang, L., Mendenhall, E., Heinz, S., Simon, I., Benner, C., & Goren, A. (2025). Improved spike-in normalization clarifies the relationship between active histone modifications and transcription. Genomics. https://doi.org/10.1101/2025.11.25.690627 Xu, T., Wang, J., Shin, Y., Cao, Y., Zhang, L., Modolo, E., Dishon, T., Fisher, J., Norton, M., Fry, C. J., Farjoun, Y., Mendenhall, E., Heinz, S., Benner, C., & Goren, A. (2026). Multiplexed measurements of protein-protein interactions and protein abundance across cellular conditions using Prod&PQ-seq. Genomics. https://doi.org/10.64898/2026.01.01.697286 Related Episodes Taking ChIP from Yeast to ENCODE to Enable Genome-Wide Regulatory Protein Mapping (Peggy Farnham) Comparing CUT&Tag to ENCODE ChIP-Seq in Alzheimer's Disease Samples (Sarah Marzi) Chromatin Profiling: From ChIP to CUT&RUN, CUT&Tag and CUTAC (Steven Henikoff) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Long-Term Maintenance of Neuronal Identity (Tomohisa Toda)

In this episode of the Epigenetics Podcast, we talked with Tomohisa Toda from the Max-Planck-Zentrum für Physik und Medizin about his work on the long-term maintenance of neuronal identity, with a focus on epigenetic and RNA-based mechanisms in brain stability and aging. Dr. Toda describes how brain circuits are stabilized over time, why critical periods are temporally restricted, and how epigenetic regulation may help maintain established neural identity. This led him to postdoctoral work on neural stem cells and long-term maintenance. We cover his work on nuclear pore and nuclear lamina proteins, including NUP153 and Lamin B1. He explains that NUP153 is enriched in neural stem cells and appears to act as a platform for recruiting factors that help maintain the stem cell epigenome. For Lamin B1, we discuss its decline during aging, how its loss can lead to stem cell exhaustion, reduced adult neurogenesis, and age-related mood dysregulation in the hippocampus. We also discuss LINE-1 RNA, where we learn that reducing LINE-1 promotes neural progenitor differentiation. He explains that this effect is linked to the RNA sequence itself rather than retrotransposition, based on rescue experiments. Finally, we talk about his finding that a subset of postnatally born brain cells contains nuclear RNAs that remain detectable for up to two years. He describes their nuclear enrichment, possible association with heterochromatin, and ongoing work to understand their sequence features, modifications, and biological function. References Bedrosian, T. A., Houtman, J., Eguiguren, J. S., Ghassemzadeh, S., Rund, N., Novaresi, N. M., Hu, L., Parylak, S. L., Denli, A. M., Randolph-Moore, L., Namba, T., Gage, F. H., & Toda, T. (2021). Lamin B1 decline underlies age-related loss of adult hippocampal neurogenesis. The EMBO journal, 40(3), e105819. https://doi.org/10.15252/embj.2020105819 Zocher, S., McCloskey, A., Karasinsky, A., Schulte, R., Friedrich, U., Lesche, M., Rund, N., Gage, F. H., Hetzer, M. W., & Toda, T. (2024). Lifelong persistence of nuclear RNAs in the mouse brain. Science (New York, N.Y.), 384(6691), 53–59. https://doi.org/10.1126/science.adf3481 Zhilina, D., Bolaños Castro, L. A., Eguiguren, J. S., Zocher, S., Karasinsky, A., Widmer, D., Espinós, A., Borrell, V., Brand, M., Miura, K., Zierau, O., Yun, M. H., & Toda, T. (2026). Dynamic expression of lamin B1 during adult neurogenesis in the vertebrate brain. Developmental dynamics : an official publication of the American Association of Anatomists, 255(2), 187–208. https://doi.org/10.1002/dvdy.70023 Related Episodes Characterizing Chromatin at the Nuclear Lamina (Bas van Steensel) Single Cell Epigenomics in Neuronal Development (Tim Petros) The Role of Histone Dopaminylation and Serotinylation in Neuronal Plasticity (Ian Maze) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Enhancer RNAs: Discovery and Function (Tae-Kyung Kim)

In this episode of the Epigenetics Podcast, we talked with Tae-Kyung Kim from POSTECH in South Korea about the discovery and characterisation of enhancer RNAs. Dr. Kim describes joining Danny Reinberg’s lab as a graduate student, where he was trained in protein biochemistry and general transcription mechanisms. He recalls this period as a formative time, when research on transcription factors and RNA polymerase II was rapidly advancing and many findings were still novel. Kim then moved into neurobiology through Michael Greenberg’s lab, where he first worked on a project related to L-type voltage-gated channels. He says his work shifted toward chromatin and gene regulation in neurons after learning that chromatin immunoprecipitation could be applied to neuronal systems and after the arrival of next-generation sequencing. He explains that eRNAs were discovered in his lab through RNA-seq and ChIP-seq data from neuronal activity experiments, especially around the FOS locus. He later showed that eRNAs are transcribed from enhancers, are typically unstable, often lack splicing and polyadenylation, and have defined initiation sites, suggesting regulated transcription. Kim says eRNAs can interact with transcription and epigenetic regulators, including factors involved in pause release and mediator complexes. He describes experiments showing that eRNA knockdown reduced ARC induction and that eRNA production depends on proper enhancer-promoter contact. He concludes by describing newer work in his lab using spatial transcriptomics and eRNA-based reporter systems to map active neural populations, including studies related to cocaine-responsive circuits. He says his future work will focus on spatial technologies to better understand brain organization and function at molecular resolution. References Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME. Widespread transcription at neuronal activity-regulated enhancers. Nature. 2010 May 13;465(7295):182-7. doi: 10.1038/nature09033. Epub 2010 Apr 14. PMID: 20393465; PMCID: PMC3020079. Schaukowitch K, Joo JY, Liu X, Watts JK, Martinez C, Kim TK. Enhancer RNA facilitates NELF release from immediate early genes. Mol Cell. 2014 Oct 2;56(1):29-42. doi: 10.1016/j.molcel.2014.08.023. Epub 2014 Sep 25. PMID: 25263592; PMCID: PMC4186258. Kim SK, Liu X, Park J, Um D, Kilaru G, Chiang CM, Kang M, Huber KM, Kang K, Kim TK. Functional coordination of BET family proteins underlies altered transcription associated with memory impairment in fragile X syndrome. Sci Adv. 2021 May 19;7(21):eabf7346. doi: 10.1126/sciadv.abf7346. PMID: 34138732; PMCID: PMC8133748. Gorbovytska V, Kim SK, Kuybu F, Götze M, Um D, Kang K, Pittroff A, Brennecke T, Schneider LM, Leitner A, Kim TK, Kuhn CD. Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF. Nat Commun. 2022 May 4;13(1):2429. doi: 10.1038/s41467-022-29934-w. PMID: 35508485; PMCID: PMC9068813. Related Episodes Enhancer Communities in Adipocyte Differentiation (Susanne Mandrup) Enhancer-Promoter Interactions During Development (Yad Ghavi-Helm) Enhancers and Chromatin Remodeling in Mammary Gland Development (Camila dos Santos) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Peter Becker: A Career in Chromatin — From ISWI to Dosage Compensation

In this episode of the Epigenetics Podcast, we talked with Peter Becker from the Biomedical Center Munich about his successful career in Epigenetics, where he discovered the chromatin remodeler ISWI and dosage compensation complex MOF. Dr. Becker shares thoughts about his postdoctoral work with Carl Wu, where he developed embryo extract systems for studying chromatin assembly and transcription. He explains how work on Drosophila extracts led to the purification of ATP-dependent remodeling factors, including ISWI-related complexes, and how these studies showed that such factors slide nucleosomes and help organize chromatin. We also cover his move to EMBL and later to Munich, where his lab expanded into dosage compensation in Drosophila. He describes work on the MSL complex targeting, MRE sequences, ROX RNA, DNA shape features, and how biochemical reconstitution was used to study how the complex recognizes the X chromosome. Finally, we discuss his later work on TIP-60 and histone acetylation, including acetylome studies, and his reflections on leadership roles at EMBL and on the use of the term epigenetics. He emphasizes that epigenetics should be understood as one layer among genetics, environment, and socialization, not as a replacement for genetics. References Tsukiyama, T., Becker, P. B., & Wu, C. (1994). ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature, 367(6463), 525–532. https://doi.org/10.1038/367525a0 Varga-Weisz, P. D., Wilm, M., Bonte, E., Dumas, K., Mann, M., & Becker, P. B. (1997). Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II. Nature, 388(6642), 598–602. https://doi.org/10.1038/41587 Corona, D. F., Längst, G., Clapier, C. R., Bonte, E. J., Ferrari, S., Tamkun, J. W., & Becker, P. B. (1999). ISWI is an ATP-dependent nucleosome remodeling factor. Molecular cell, 3(2), 239–245. https://doi.org/10.1016/s1097-2765(00)80314-7 Akhtar, A., & Becker, P. B. (2000). Activation of transcription through histone H4 acetylation by MOF, an acetyltransferase essential for dosage compensation in Drosophila. Molecular cell, 5(2), 367–375. https://doi.org/10.1016/s1097-2765(00)80431-1 Akhtar, A., Zink, D., & Becker, P. B. (2000). Chromodomains are protein-RNA interaction modules. Nature, 407(6802), 405–409. https://doi.org/10.1038/35030169 Villa, R., Schauer, T., Smialowski, P., Straub, T., & Becker, P. B. (2016). PionX sites mark the X chromosome for dosage compensation. Nature, 537(7619), 244–248. https://doi.org/10.1038/nature19338 Related Episodes Dosage Compensation in Drosophila (Asifa Akhtar) DNase Hypersensitive Sites and Chromatin Remodeling Enzymes (Carl Wu) The Mechanism of ATP-dependent Remodelers and HP1 Gene Silencing (Geeta Narlikar) Regulation of Chromatin Organization by Histone Chaperones (Geneviève Almouzni) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Transcriptional and Epigenetic Regulation of Craniofacial Development (Filippo Rijli)

In this episode of the Epigenetics Podcast, we talked with Filippo Rijli from the Friedrich Miescher Institute about his work on transcriptional and epigenetic regulation of craniofacial and neuronal development. Dr. Rijli recalls pivotal moments in his career, including his postdoctoral work where he explored the functions of HoxA2 in craniofacial development. We discuss key findings from his landmark papers, highlighting how individual transcription factors like HoxA2 can dictate the topographic organization of neuronal circuits. His exploration of the whisker-to-barrel cortex circuit in mice unveils how sensory inputs are mapped and processed through precise neuronal connections. This intricate mapping reveals how singular genes can impact the wiring of entire neurological systems. We also reflect on the evolution of scientific communication throughout Filippo’s career, from the reliance on faxes and handwritten requests for paper reprints to today's instant access to research through digital platforms. His early experiences have instilled in him a resourcefulness that continues to inform his approach to research, particularly in environments with limited resources where collaboration becomes essential. Our discussion shifts to his recent research endeavors that delve into transcriptional and epigenetic regulation during neuronal and craniofacial development. Dr. Rijli elaborates on a 2015 study which demonstrated how the ectopic expression of HoxA2 could lead to the creation of artificial whisker maps in the brain, providing insights into how transcription factors guide neuronal behavior and circuit formation. His work on the histone methyltransferase EZH2 reveals its crucial role in the tangential migration of cerebellar neurons and the mechanisms that ensure these neurons reach their accurate destinations during development. Dr. Rijli's research further investigates the chromatin landscape of cranial neural crest cells, uncovering how polycomb group proteins maintain a poised state that enables these cells to respond flexibly to environmental signals. This concept of plasticity is particularly relevant in his latest research on nasal chondrocytes, suggesting that these cells retain developmental potential that may be harnessed in regenerative medicine. The discussions hint at a future where understanding these intricate mechanisms could lead to groundbreaking advancements in treating injuries or diseases. Throughout the episode, Dr. Rijli’s enthusiasm for discovery is palpable as he shares how each research finding leads to more questions, showcasing the iterative nature of scientific research. This dialogue provides not only a deep dive into his specific studies but also a broader view of how developmental biology continues to evolve, emphasizing the importance of understanding the molecular underpinnings of cellular identity and connectivity. References Oury, F., Murakami, Y., Renaud, J. S., Pasqualetti, M., Charnay, P., Ren, S. Y., & Rijli, F. M. (2006). Hoxa2- and rhombomere-dependent development of the mouse facial somatosensory map. Science (New York, N.Y.), 313(5792), 1408–1413. https://doi.org/10.1126/science.1130042 Di Meglio, T., Kratochwil, C. F., Vilain, N., Loche, A., Vitobello, A., Yonehara, K., Hrycaj, S. M., Roska, B., Peters, A. H., Eichmann, A., Wellik, D., Ducret, S., & Rijli, F. M. (2013). Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons. Science (New York, N.Y.), 339(6116), 204–207. https://doi.org/10.1126/science.1229326 Minoux, M., Holwerda, S., Vitobello, A., Kitazawa, T., Kohler, H., Stadler, M. B., & Rijli, F. M. (2017). Gene bivalency at Polycomb domains regulates cranial neural crest positional identity. Science (New York, N.Y.), 355(6332), eaal2913. https://doi.org/10.1126/science.aal2913 Kessler, S., Minoux, M., Joshi, O., Ben Zouari, Y., Ducret, S., Ross, F., Vilain, N., Salvi, A., Wolff, J., Kohler, H., Stadler, M. B., & Rijli, F. M. (2023). A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest. Nature communications, 14(1), 3242. https://doi.org/10.1038/s41467-023-38953-0 Related Episodes Chromatin Modifiers and Their Roles in Brain Development (Fides Zenk) Exploring DNA Methylation and TET Enzymes in Early Development (Petra Hajkova) The Role of H3K4me3 in Embryonic Development (Eva Hörmanseder) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

Epigenetic Signatures During Aging and Cancer (Alena van Bömmel)

In this episode of the Epigenetics Podcast, we talked with Alena van Bömmel from the Biomedical Center (BMC) in Munich about her work on the development of interpretable epigenetic clocks and statistical models of epigenetic dynamics during aging, and the unique epigenetic signatures associated with various cancers, such as brain tumors or leukemias to detect powerful diagnostic markers or predictors of therapeutic response. The Interview starts with Dr. van Bömmel sharing her work on co-occurring transcription factors within cell-type specific enhancers, describing the pioneering use of DNA sequencing and its substantial implications in understanding chromatin accessibility. We explore the findings that revealed varying transcription factor interactions across cell types, emphasizing the complexity inherent in gene regulation. Although her research largely remained in silico, its findings paved the way for potential validation through advanced sequencing techniques. The discussion broadens to encompass Dr. van Bömmel's work on pediatric acute lymphoblastic leukemia, where she elaborates on the epigenetic dynamics observed in patient samples. We discuss her collaboration on a large project that aimed to elucidate the methylation profiles of leukemia patients and how specific epigenetic modifications might indicate cancer subtypes. As the conversation shifts towards aging, Dr. van Bömmel explains her research on DNA methylation trajectories in mouse models. This work unearthed unexpected patterns of abrupt changes in methylation that correspond to distinct life stages, reflecting the potential applicability of these findings in understanding human aging processes. Delving further into her innovative research, she introduces 'Methylizer,' a groundbreaking DNA methylation-based classifier designed for brain tumor diagnostics. We examine the rapid diagnostic capabilities this tool offers in surgical contexts, illustrating a paradigm shift in how epigenetic data can inform real-time clinical decisions. Now at the LMU in Munich, Dr. van Bömmel shares her experiences establishing her lab and her intent to foster a computational-focused research environment that collaborates closely with wet lab scientists. We discuss her aspirations to integrate various layers of epigenetic data through advanced statistical methods and to investigate the aging dynamics of brain cells, specifically in the context of neurodegenerative diseases like Alzheimer’s. References Van Bömmel, A., Love, M. I., Chung, H.-R., & Vingron, M. (2018). coTRaCTE predicts co-occurring transcription factors within cell-type specific enhancers. PLOS Computational Biology, 14(8), e1006372. https://doi.org/10.1371/journal.pcbi.1006372 Olecka, M., van Bömmel, A., Best, L., Haase, M., Foerste, S., Riege, K., Dost, T., Flor, S., Witte, O. W., Franzenburg, S., Groth, M., von Eyss, B., Kaleta, C., Frahm, C., & Hoffmann, S. (2024). Nonlinear DNA methylation trajectories in aging male mice. Nature communications, 15(1), 3074. https://doi.org/10.1038/s41467-024-47316-2 Brändl, B., Steiger, M., Kubelt, C., Rohrandt, C., Zhu, Z., Evers, M., Wang, G., Schuldt, B., Afflerbach, A. K., Wong, D., Lum, A., Halldorsson, S., Djirackor, L., Leske, H., Magadeeva, S., Smičius, R., Quedenau, C., Schmidt, N. O., Schüller, U., Vik-Mo, E. O., … Müller, F. J. (2025). Rapid brain tumor classification from sparse epigenomic data. Nature medicine, 31(3), 840–848. https://doi.org/10.1038/s41591-024-03435-3 Related Episodes Evolutionary Epigenetic Clocks and Epigenetic Inheritance in Plants (Frank Johannes) Epigenetic Clocks and Biomarkers of Ageing (Morgan Levine) Epigenetic Consequences of DNA Methylation in Development (Maxim Greenberg) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Heterochromatin Formation by the HUSH complex (Iva Tchasovnikarova)

In this episode of the Epigenetics Podcast, we talked with Iva Tchasovnikarova from the Wellcome Trust Cancer Research UK Gurdon Institute about her work on heterochromatin formation and epigenetic control. We begin with Dr. Tchasovnikarova's journey into the field of biology, tracing her roots back to her formative years and the pragmatic guidance of her parents. Despite initial uncertainty about her career path, it was her mother’s passion for teaching biology that ultimately inspired her to pursue a degree in the subject. As Dr. Tchasovnikarova introduces her current role as a group leader at the Gurdon Institute and an assistant professor at the University of Cambridge, she highlights her early work during her PhD which yielded a first-author publication in Science. She reflects on the serendipitous aspects of this experience, detailing a project where she utilised a novel genetic screening system to uncover a repressor complex named HUSH, a pivotal discovery that has implications for understanding transcriptional repression mechanisms in vertebrates. The conversation progresses into her postdoctoral research, where she further explored the HUSH complex's role alongside another complex, HUSH2. This expansion of her research reveals fascinating insights into how these complexes interact and their potential significance in regulating gene expression, particularly concerning immune responses to viral infections. Dr. Tchasovnikarova outlines her systematic approach to unraveling these complexities, emphasizing the role of reporter systems and genetic screens in uncovering uncharacterized genes and their functions. In discussing her transition to starting her own lab, Dr. Tchasovnikarova shares her excitement about utilizing methods she developed during her postdoc to discover new regulatory mechanisms. She describes specific experiments that have led to groundbreaking findings, including the characterization of CRAMP1, a regulator of linker histones, which plays a crucial role in the function of the polycomb repressive complex. The intricate relationships between these elements underscore her commitment to understanding the nuances of epigenetic regulation and genome stability. References Tchasovnikarova, I. A., Timms, R. T., Matheson, N. J., Wals, K., Antrobus, R., Göttgens, B., Dougan, G., Dawson, M. A., & Lehner, P. J. (2015). GENE SILENCING. Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science (New York, N.Y.), 348(6242), 1481–1485. https://doi.org/10.1126/science.aaa7227 Danac, J. M. C., Matthews, R. E., Gungi, A., Qin, C., Parsons, H., Antrobus, R., Timms, R. T., & Tchasovnikarova, I. A. (2024). Competition between two HUSH complexes orchestrates the immune response to retroelement invasion. Molecular cell, 84(15), 2870–2881.e5. https://doi.org/10.1016/j.molcel.2024.06.020 Related Episodes Heterochromatin Protein 1 and its Influence on the Structure of Chromatin (Serena Sanulli) Heterochromatin and Phase Separation (Gary Karpen) Polycomb and Three-Dimensional Genome Organisation (Oliver Bell) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Cryo-EM and the Dynamics of TFIID and PRC2 (Eva Nogales)

In this episode of the Epigenetics Podcast, we talked with Eva Nogales from UC Berkeley about her work on Cryo-EM and the Dynamics of TFIID and PRC2. We explore the origins of Dr. Nogales's fascination with biology and how her academic journey shifted from physics into the realms of biophysics and structural biology. She shares the profound impact of her training under physicists who instilled a rigorous, quantitative approach to problem-solving, a perspective that continues to influence her work. The importance of visualization emerges as a central theme, showcasing how critical imagery can foster understanding even amidst complex biological structures. A particular focus of our discussion centers on the transcription factor complex TFIID, a significant milestone in Dr. Nogales's career. She recalls the challenging journey to uncovering its structure for the first time, which involved navigating numerous technical hurdles. Dr. Nogales details how their innovative approaches led to insights about the conformational flexibility and functional dynamics of TFIID, especially in relation to its interactions with DNA during transcription initiation. The richness of this narrative reflects both the perseverance required in scientific discovery and the serendipity that often accompanies groundbreaking breakthroughs. Transitioning into the epigenetics realm, Dr. Nogales elucidates the critical role of PRC2 in gene silencing and cellular identity preservation. With a focus on chromatin and nucleosome interactions, we unpack the intricate mechanisms by which PRC2 functions in the context of chromatin remodeling and gene regulation. Dr. Nogales recounts how collaborations and the imaginative contributions of her lab members led to novel research trajectories, particularly the elucidation of structural states of PRC2 bound to chromatin and characterized by novel methodologies developed within her lab. Further, our discussion touches on Dr. Nogales’s recent findings regarding the nuanced interplay of various cofactors involved in PRC2's regulatory functions. We delve into her exciting projects aiming to bring further clarity to the complex dynamics of chromatin interaction and the distinct forms of PRC2. Dr. Nogales's unyielding commitment to research is mirrored in her ambition to explore unresolved questions surrounding these multifaceted biological processes. References Andel F 3rd, Ladurner AG, Inouye C, Tjian R, Nogales E. Three-dimensional structure of the human TFIID-IIA-IIB complex. Science. 1999 Dec 10;286(5447):2153-6. doi: 10.1126/science.286.5447.2153. PMID: 10591646. Cianfrocco MA, Kassavetis GA, Grob P, Fang J, Juven-Gershon T, Kadonaga JT, Nogales E. Human TFIID binds to core promoter DNA in a reorganized structural state. Cell. 2013 Jan 17;152(1-2):120-31. doi: 10.1016/j.cell.2012.12.005. PMID: 23332750; PMCID: PMC3552382. Yang Z, Mameri A, Cattoglio C, Lachance C, Florez Ariza AJ, Luo J, Humbert J, Sudarshan D, Banerjea A, Galloy M, Fradet-Turcotte A, Lambert JP, Ranish JA, Côté J, Nogales E. Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex. Science. 2024 Aug 23;385(6711):eadl5816. doi: 10.1126/science.adl5816. Epub 2024 Aug 23. PMID: 39088653. Related Episodes Structural Analysis of Nucleosomes During Transcription (Lucas Farnung) Molecular Mechanisms of Chromatin Modifying Enzymes (Karim-Jean Armache) From Nucleosome Structure to Function (Karolin Luger) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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RNA modifications and Gene Expression (Michaela Frye)

In this episode of the Epigenetics Podcast, we talked with Michaela Frye from he German Cancer Research Center (DKFZ) in Heidelberg about her work on the role of RNA modifications and RNA binding proteins in gene expression and cancer development. Central to Dr. Frey’s work is the NSUN family of RNA-modifying proteins, which she first encountered during her postdoctoral research. Initially perceived as a DNA methyltransferase, she unwittingly discovered that this family also plays vital roles in RNA methylation. Her exploration revealed that these proteins significantly affect gene stability and translation processes, especially under stress, making them critical players in cancer pathology. As her research progressed, Frey transitioned into her own lab, where she continued exploring RNA modifications in the context of skin and cancer cells. She emphasizes the critical distinction between the roles of different RNA modifications in various cellular contexts, especially highlighting the differences between steady-state stem cells and those undergoing differentiation or stress responses. Frey's lab investigates how these modifications regulate translational processes, which are essential for cellular adaptation to environmental changes. Frey further discusses her findings related to the NSUN proteins in stem cell function and their implications for germ cell differentiation in testes. This intricate relationship between RNA modifications and cellular dynamics underscores the significance of epitranscriptomics in understanding cancer treatment resistance and cellular adaptation mechanisms. Recent findings from her team at DKFZ show a compelling connection between mitochondrial function and RNA modifications in cancer cells. Frey articulates a newfound interest in how these modifications influence cellular responses to cancer therapies, particularly how their regulation may mitigate treatment resistance. Reflecting on the evolution of RNA modification research, she notes that the field has matured rapidly but acknowledges the challenges posed by abundant yet often contradictory findings. Frey advocates for a clearer understanding of the fundamental functions of distinct RNA modifications to harness their potential in therapeutic contexts effectively. References Blanco S, Kurowski A, Nichols J, et al. The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. Plos Genetics. 2011 Dec;7(12):e1002403. DOI: 10.1371/journal.pgen.1002403. PMID: 22144916; PMCID: PMC3228827 Hussain S, Tuorto F, Menon S, et al. The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the chromatoid body and required for testis differentiation. Molecular and Cellular Biology. 2013 Apr;33(8):1561-1570. DOI: 10.1128/mcb.01523-12. PMID: 23401851; PMCID: PMC3624257 Blanco S, Bandiera R, Popis M, et al. Stem cell function and stress response are controlled by protein synthesis. Nature. 2016 Jun;534(7607):335-340. DOI: 10.1038/nature18282. PMID: 27306184; PMCID: PMC5040503 Delaunay S, Pascual G, Feng B, et al. Mitochondrial RNA modifications shape metabolic plasticity in metastasis. Nature. 2022 Jul;607(7919):593-603. DOI: 10.1038/s41586-022-04898-5. PMID: 35768510; PMCID: PMC9300468. Related Episodes The Effect of lncRNAs on Chromatin and Gene Regulation (John Rinn) The Role of lncRNAs in Tumor Growth and Treatment (Sarah Diermeier) The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Polycomb and Three-Dimensional Genome Organisation (Oliver Bell)

In this episode of the Epigenetics Podcast, we talked with Oliver Bell from the University of Southern California in Los Angeles about his work on chromatin-based regulatory systems that encode cellular memory and their implications for development and disease. The Interview starts with Dr. Bell describing his early career contributions to understanding the functionality of histone methylation in facilitating dosage compensation and gene silencing. His efforts at dissecting the complexities of epigenetic regulation culminate in significant discoveries that highlight the nuanced effects of chromatin adjustments on gene activity and stability across cell divisions. As we progress, Dr. Bell shares details about his postdoctoral research, where he engineered systems to study chromatin remodeling and the maintenance of transcriptional states through development. His innovative use of induced proximity to manipulate chromatin modifiers offers groundbreaking approaches to understanding how epigenetic states can be established and sustained, alongside the implications for therapeutic strategies in cancer treatment. An important aspect of our discussion centers on his identification of the ZFP462 protein, which plays a critical role in neurodevelopmental disorders. Dr. Bell outlines his lab's ongoing research into deciphering how this zinc finger protein interacts with enhancers to influence gene regulation in embryonic stem cells and its potential connection to specific diseases. This leads to an engaging dialogue about the relationship between 3D genome organization and epigenetic regulation, focusing on how disruptions in chromatin architecture may affect gene expression. Towards the end of our conversation, we touch upon the emerging potential of AI in epigenetic research, exploring how advances in technology could facilitate the screening of small molecules targeted at chromatin-modifying complexes. Dr. Bell offers a forward-looking perspective on the future applications of this research, revealing his aspirations for therapeutic developments based on his findings. References Bell, O., Wirbelauer, C., Hild, M., Scharf, A. N., Schwaiger, M., MacAlpine, D. M., Zilbermann, F., van Leeuwen, F., Bell, S. P., Imhof, A., Garza, D., Peters, A. H., & Schübeler, D. (2007). Localized H3K36 methylation states define histone H4K16 acetylation during transcriptional elongation in Drosophila. The EMBO journal, 26(24), 4974–4984. https://doi.org/10.1038/sj.emboj.7601926 Hathaway, N. A., Bell, O., Hodges, C., Miller, E. L., Neel, D. S., & Crabtree, G. R. (2012). Dynamics and memory of heterochromatin in living cells. Cell, 149(7), 1447–1460. https://doi.org/10.1016/j.cell.2012.03.052 Moussa, H. F., Bsteh, D., Yelagandula, R., Pribitzer, C., Stecher, K., Bartalska, K., Michetti, L., Wang, J., Zepeda-Martinez, J. A., Elling, U., Stuckey, J. I., James, L. I., Frye, S. V., & Bell, O. (2019). Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing. Nature communications, 10(1), 1931. https://doi.org/10.1038/s41467-019-09628-6 Yelagandula, R., Stecher, K., Novatchkova, M. et al. ZFP462 safeguards neural lineage specification by targeting G9A/GLP-mediated heterochromatin to silence enhancers. Nat Cell Biol 25, 42–55 (2023). https://doi.org/10.1038/s41556-022-01051-2 Bsteh, D., Moussa, H.F., Michlits, G. et al. Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops. Nat Commun 14, 8160 (2023). https://doi.org/10.1038/s41467-023-43869-w Related Episodes Effects of DNA Methylation on Chromatin Structure and Transcription (Dirk Schübeler) Polycomb Proteins, Gene Regulation, and Genome Organization in Drosophila (Giacomo Cavalli) Transcription and Polycomb in Inheritance and Disease (Danny Reinberg) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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From Placeholder Nucleosomes to Zygotic Genome Activation (Patrick Murphy)

In this episode of the Epigenetics Podcast, we talked with Patrick Murphy from Cornell University about his work on gene regulation and cellular identity. Dr. Murphy's research focuses on the molecular mechanisms that govern gene expression through transcriptional and chromatin-based regulatory networks. At the start of the Interview Dr. Murphy describes an innovative single-molecule analytical approach he developed during his early research. This method enables the simultaneous detection of multiple epigenetic marks and contributes to his foundational studies on chromatin biology. Focusing on chromatin states, he introduces the concept of placeholder nucleosomes which are specialised nucleosomes that play key roles in maintaining a permissive chromatin state and facilitating gene activation during embryonic development. The discussion further explores Dr. Murphy's transition from studying Drosophila to working with zebrafish, highlighting his focus on chromatin reprogramming during zygotic genome activation. He presents data from his collaborations that reveal intriguing roles for specific chromatin marks, emphasising how these discoveries hold potential for understanding gene expression regulation in both zebrafish and mammalian models. Dr. Murphy also shares insights into a project investigating the impacts of paternal cigarette smoke on offspring health, which led to an exploration of systemic inflammation responses and their lasting effects on gene expression in the brain. This unique intersection of basic and translational research underlines the wide-ranging implications of his findings. References Murphy, P. J., Cipriany, B. R., Wallin, C. B., Ju, C. Y., Szeto, K., Hagarman, J. A., Benitez, J. J., Craighead, H. G., & Soloway, P. D. (2013). Single-molecule analysis of combinatorial epigenomic states in normal and tumor cells. Proceedings of the National Academy of Sciences of the United States of America, 110(19), 7772–7777. https://doi.org/10.1073/pnas.1218495110 Murphy, P. J., Wu, S. F., James, C. R., Wike, C. L., & Cairns, B. R. (2018). Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming. Cell, 172(5), 993–1006.e13. https://doi.org/10.1016/j.cell.2018.01.022 Park, B. J., Hua, S., Casler, K. D., Cefaloni, E., Ayers, M. C., Lake, R. F., Murphy, K. E., Vertino, P. M., O'Connell, M. R., & Murphy, P. J. (2025). CUT&Tag overcomes biases of ChIP and establishes chromatin patterns for repetitive genomic loci. iScience, 28(11), 113757. https://doi.org/10.1016/j.isci.2025.113757 Related Episodes Pioneer Transcription Factors and Their Influence on Chromatin Structure (Ken Zaret) In Vivo Nucleosome Structure and Dynamics (Srinivas Ramachandran) Nucleosome Positioning in Cancer Diagnostics (Vladimir Teif) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Decoding Cell Fate Through 3D Genome Organization and Chromatin Dynamics (Srinjan Basu)

In this episode of the Epigenetics Podcast, we talked with Srinjan Basu from Imperial College London to talk about his work on how chromatin architecture and epigenetic mechanisms orchestrate developmental gene expression programs. We begin by exploring Dr. Basu's early work at Harvard which involved pioneering Raman-based label-free imaging, allowing the study of chromatin dynamics in live tissue. Here, he tackles technical challenges faced in visualizing DNA interactions, emphasizing the shift from 2D to 3D analysis and the importance of real-time observation of chromatin behavior under various conditions. This segues into his groundbreaking research on single transcription factors interacting with chromatin, revealing subtle but significant changes in the dynamics of gene regulation. We transition into the complexities of chromatin architecture as Dr. Basu recounts his efforts in mapping the entire mouse genome in single pluripotent cells, unearthing unexpected heterogeneity among cells. This heterogeneity raises intriguing questions about its impact on cellular function, prompting ongoing investigations into chromatin dynamics and the role of remodeling complexes like NuRD in cell fate transitions. Dr. Basu elucidates how recent studies have begun to bridge the gaps in understanding how transcription factors and chromatin dynamics interact during cellular decisions, particularly emphasizing the influence of mechanical signals and the intrinsic properties of cells. His research underscores the idea that stem cells undergo a preparatory phase for differentiation, highlighting the critical balance of intrinsic and extrinsic factors that govern genetic expression and cellular outcomes. We also talk about Dr. Basu's current research trajectory, focusing on enhancing imaging techniques to study gene dynamics in tissue contexts relevant to developmental biology and disease states. He illustrates a vision for future projects that integrate advanced imaging tools to investigate transcription factor dynamics and chromatin interactions in live cells and embryos, furthering the understanding of decision-making processes in cellular contexts. References Stevens TJ, Lando D, Basu S, et al. 3D structures of individual mammalian genomes studied by single-cell Hi-C. Nature. 2017 Apr;544(7648):59-64. DOI: 10.1038/nature21429. PMID: 28289288; PMCID: PMC5385134. Basu S, Needham LM, Lando D, et al. FRET-enhanced photostability allows improved single-molecule tracking of proteins and protein complexes in live mammalian cells. Nature Communications. 2018 Jun;9(1):2520. DOI: 10.1038/s41467-018-04486-0. PMID: 29955052; PMCID: PMC6023872. Related Episodes Advanced Optical Imaging in 3D Nuclear Organisation (Lothar Schermelleh) Analysis of 3D Chromatin Structure Using Super-Resolution Imaging (Alistair Boettiger) Single-Molecule Imaging of the Epigenome (Efrat Shema) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Taking ChIP from Yeast to ENCODE to Enable Genome-Wide Regulatory Protein Mapping (Peggy Farnham)

In this episode of the Epigenetics Podcast, we talked with Peggy Farnham from the Keck School of Medicine at USC about her work on establishing the ChIP Method in mammalian cells. In this episode, we dive into the relationship between transcription factors, chromatin dynamics, and gene expression with Professor Peggy Farnham from the Keck School of Medicine at USC. Professor Farnham shares her profound insights into how her groundbreaking research has reshaped our understanding of gene regulation and its implications in cancer. We explore how she has been a pioneer in mapping the genome-wide landscape of regulatory proteins, illuminating the molecular logic behind transcriptional control and its disruption in cancer biology. The interview starts with her instrumental role in adapting chromatin immunoprecipitation (ChIP) technology from yeast to human cells. Professor Farnham reflects on the technical challenges she faced during this transition, such as the quest for visibility of signals in mammalian systems. Her ability to innovate and troubleshoot challenges led to significant advancements in techniques that allow for the rapid identification of transcription factor binding sites, fundamentally changing the landscape of epigenetic research. As the discussion progresses, we learn about Professor Farnham's active involvement in the ENCODE project, where she contributed to high-resolution mapping of transcription factors and regulatory elements in human cells. She articulates her appreciation for collaborative efforts in science, highlighting how working within a consortium harnesses the collective expertise of diverse research groups. This collaboration not only bolstered the credibility of the data produced but also propelled the field forward in understanding the complexity of gene regulation. Through her participation in various projects, such as the Psyc-ENCODE consortium and the Roadmap Epigenome Mapping Consortium, Professor Farnham shares insights into her investigation of epigenetic variations, particularly in relation to complex disorders like schizophrenia. Her findings underscore the nuances of enhancer variability among individuals and the implications for understanding disease mechanisms, thereby advancing our knowledge of genetic regulation and its contributions to diverse biological outcomes. Moreover, the episode highlights Professor Farnham's reflective understanding of emerging technologies in the field. She discusses the evolution of methods that allow researchers to investigate gene regulation at single-cell resolution, recognizing the significant implications these innovations have for our comprehension of cellular differentiation and the transcriptional landscape. References Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ. Use of chromatin immunoprecipitation to clone novel E2F target promoters. Molecular and Cellular Biology. 2001 Oct;21(20):6820-6832. DOI: 10.1128/mcb.21.20.6820-6832.2001. PMID: 11564866; PMCID: PMC99859. Wells J, Farnham PJ. Characterizing transcription factor binding sites using formaldehyde crosslinking and immunoprecipitation. Methods (San Diego, Calif.). 2002 Jan;26(1):48-56. DOI: 10.1016/s1046-2023(02)00007-5. PMID: 12054904. Rhie SK, Schreiner S, Witt H, et al. Using 3D epigenomic maps of primary olfactory neuronal cells from living individuals to understand gene regulation. Science Advances. 2018 Dec;4(12):eaav8550. DOI: 10.1126/sciadv.aav8550. PMID: 30555922; PMCID: PMC6292713. Tak YG, Hung Y, Yao L, et al. Effects on the transcriptome upon deletion of a distal element cannot be predicted by the size of the H3K27Ac peak in human cells. Nucleic Acids Research. 2016 May;44(9):4123-4133. DOI: 10.1093/nar/gkv1530. PMID: 26743005; PMCID: PMC4872074. Related Episodes The Effect of lncRNAs on Chromatin and Gene Regulation (John Rinn) CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird) The Future of Protein–DNA Mapping (Mitch Guttman) MLL Proteins in Mixed-Lineage Leukemia (Yali Dou) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Spatial-Omics and Machine Learning in Muscle Stem Cell Repair (Will Wang)

In this episode of the Epigenetics Podcast, we talked with Will Wang from Sanford Burnham Prebys about his work on muscle stem cell repair, regeneration, and aging, exploring spatial-omics and machine learning. We begin our conversation by exploring the traditional concepts of spatial biology and how they have evolved to play a critical role in disease research. Dr. Wang recounts his journey from a young student in a family of academics to becoming a leading figure in regenerative biology, highlighting how his early interests in life sciences, natural problem-solving abilities, and inspirations from mentorship set the stage for his current research trajectory. Throughout the discussion, we uncover key insights on how muscle stem cells transition from a quiescent state to a proliferative state in response to injury and how this dynamic process is governed by the epigenetic landscape and various signalling pathways. Dr. Wang emphasises the impact of external factors—be it microenvironment conditions or metabolic cues—on the fate and function of these stem cells, reflecting on the methodologies used to investigate these processes throughout his career. He shares fascinating findings from his PhD work, where he explored the regulatory role of transcription factors like PAX-7 in muscle stem cell activation, and how subsequent research developed in his postdoc at Stanford further illuminated the relationship between metabolism and histone acetylation. This pivotal work not only demonstrated how metabolic states dictate epigenetic modifications but also offered potential therapeutic insights for muscle degeneration and repair. As we move into more recent projects, Dr. Wang discusses the advances in multiplexed spatial proteomics and the insights garnered from a single-cell spatiotemporal atlas of muscle regeneration, which highlight the cellular heterogeneity in muscle tissue. He describes the use of novel computational tools, including neural networks, to uncover the regulatory mechanisms underlying stem cell function, particularly how prostaglandin signalling informs the regeneration process and how age impacts stem cell efficacy. The episode then wraps up with an engaging dialogue about the future implications of Dr. Wang’s work in addressing age-related muscle degradation and broader applications in regenerative medicine. References Yucel, N., Wang, Y. X., Mai, T., Porpiglia, E., Lund, P. J., Markov, G., Garcia, B. A., Bendall, S. C., Angelo, M., & Blau, H. M. (2019). Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function. Cell Reports, 27(13), 3939-3955.e6. https://doi.org/10.1016/j.celrep.2019.05.092 Wang, Y. X., Palla, A. R., Ho, A. T. V., Robinson, D. C. L., Ravichandran, M., Markov, G. J., Mai, T., Still, C., Balsubramani, A., Nair, S., Holbrook, C. A., Yang, A. V., Kraft, P. E., Su, S., Burns, D. M., Yucel, N. D., Qi, L. S., Kundaje, A., & Blau, H. M. (2025). Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength. Cell Stem Cell, 32(7), 1154-1169.e9. https://doi.org/10.1016/j.stem.2025.05.012 Related Episodes Stem Cell Transcriptional Regulation in Naive vs. Primed Pluripotency (Christa Buecker) The Effect of Mechanotransduction on Chromatin Structure and Transcription in Stem Cells (Sara Wickström) Epigenetic Regulation of Stem Cell Self-Renewal and Differentiation (Peggy Goodell) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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The Future of Protein–DNA Mapping (Mitch Guttman)

In this episode of the Epigenetics Podcast, we talked with Mitch Guttman from Caltec about ChIP-DIP (ChIP-Done In Parallel). ChIP-DIP is a newly developed approach for high-resolution protein–DNA interaction mapping. The method uses antibody-guided isolation of denaturant-insoluble protein–DNA complexes, resulting in substantially improved specificity and peak definition compared with conventional ChIP-seq. We explore why denaturation resistance is central to the workflow, how the method performs across transcription factors, chromatin regulators, and histone marks, and what experimental parameters determine its success. The conversation also covers current limitations, practical adoption details, and perspectives on how ChIP-DIP fits into the broader landscape of chromatin profiling technologies. References Perez, A. A., Goronzy, I. N., Blanco, M. R., Yeh, B. T., Guo, J. K., Lopes, C. S., Ettlin, O., Burr, A., & Guttman, M. (2024). ChIP-DIP maps binding of hundreds of proteins to DNA simultaneously and identifies diverse gene regulatory elements. Nature genetics, 56(12), 2827–2841. https://doi.org/10.1038/s41588-024-02000-5 Ramani, V. Split-pool barcoding serves up an epigenomic smorgasbord. Nat Genet 56, 2596–2597 (2024). https://doi.org/10.1038/s41588-024-01980-8 Related Episodes Split-Pool Recognition of Interactions by Tag Extension (SPRITE) (Mitch Guttman) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

Chromatin Modifiers and Their Roles in Brain Development (Fides Zenk)

In this episode of the Epigenetics Podcast, we talked with Fides Zenk from the École polytechnique fédérale de Lausanne about her work on transgenerational inheritance in Drosophila and brain organoids for human development insights. Dr. Zenk begins by sharing her journey into the field of biology, revealing her childhood fascination with nature and the intricate details of plant development. Her transition from an interest in ecology to a deep dive into molecular biology and gene regulation lays the groundwork for understanding her current research focus. We explore how her early experiences continue to shape her scientific curiosity, particularly her passion for studying cellular changes over time during embryonic development. As the conversation progresses, Dr. Zenk paints a vivid picture of her work at EPFL, where she combines functional genomics, chromatin profiling, and molecular biology techniques. She elaborates on her initial research during her PhD with Nicola Iovino, where she investigated the transgenerational inheritance of histone modifications in Drosophila. This discussion includes fascinating insights into how histone modifications can carry information across generations and their implications in gene expression regulation during early embryonic stages. Dr. Zenk also provides a glimpse into her postdoctoral work with Barbara Treutlein, where she shifted focus to human models and quantitative analysis using brain organoids. This segment of the episode reveals her commitment to translating molecular mechanisms to human health, especially in understanding the intricacies of brain development and neurogenesis. She describes how her team mapped dynamic changes in histone modifications during critical developmental stages, integrating various data modalities to build an intricate developmental atlas. References Zenk F, Loeser E, Schiavo R, et al. Germ line-inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition. Science (New York, N.Y.). 2017 Jul;357(6347):212-216. DOI: 10.1126/science.aam5339. PMID: 28706074. Zenk F, Zhan Y, Kos P, et al. HP1 drives de novo 3D genome reorganization in early Drosophila embryos. Nature. 2021 May;593(7858):289-293. DOI: 10.1038/s41586-021-03460-z. PMID: 33854237; PMCID: PMC8116211. Zenk F, Fleck JS, Jansen SMJ, et al. Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems. Nature Neuroscience. 2024 Jul;27(7):1376-1386. DOI: 10.1038/s41593-024-01652-0. PMID: 38914828; PMCID: PMC11239525. Related Episodes The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi) Mapping the Epigenome: From Arabidopsis to the Human Brain (Joseph Ecker) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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Region Capture Micro-C and 3D Genome Structure (Anders Sejr Hansen)

In this episode of the Epigenetics Podcast, we talked with Anders Sejr Hansen from MIT about his work on the impact of 3D genome structures on gene expression, the roles of proteins like CTCF and cohesin, and advanced techniques like Region Capture Micro-C for mapping genome organisation. Dr. Sejr Hansen introduces his research focusing on the relationship between three-dimensional genome structure and function, specifically how these structures can influence gene expression. He elaborates on the importance of transcription factors and the role of looping structures in gene regulation, emphasizing the implications of his work for understanding gene functionality in the context of both development and disease. The conversation then shifts to discussing loop extrusion and the factors affecting loop stability, primarily CTCF and cohesin. Dr. Sejr Hansen highlights the dynamics of these proteins' binding interactions and how their speeds challenge the notion of stable looping structures in the genome. With a keen interest in CTCF's role, he explains how the protein interacts with DNA and the mechanistic aspects of transcription factor movement, alluding to research findings that reveal that CTCF and cohesin tend to form clusters which may play vital roles in establishing chromatin structure. As the interview progresses, Dr. Sejr Hansen details his transition to leading his own lab at MIT, emphasizing the continuation of his earlier work while expanding into new methodologies for studying chromatin. He underscores the importance of understanding not just the static structures of DNA interactions, but the dynamic nature of these relationships and how they influence gene expression. His lab's recent focus has included using advanced imaging techniques to assess the dynamics of chromatin interactions more precisely. The discussion then touches on specific findings from Dr. Sejr Hansen's lab regarding the relationship between genome organization and double-strand break repair mechanisms. He emphasizes how the repair machinery can affect chromatin structure and underscores the essential role of cohesin in facilitating effective double-strand break repair by keeping broken DNA ends in proximity. He suggests that loop extrusion might help prevent genetic material from diffusing too far apart and improve the efficiency of repair. Dr. Sejr Hansen also discusses innovations in genome mapping techniques, particularly the development of Region Capture Micro-C, which facilitates deeper insights into the three-dimensional organization of the genome. This method allows researchers to achieve significantly higher resolution in their analyses compared to traditional 3D genomics techniques like Hi-C. He outlines the technical process and the implications of their findings, especially regarding enhancer-promoter interactions and the surprisingly promiscuous nature of these relationships. References Anders S Hansen, Iryna Pustova, Claudia Cattoglio, Robert Tjian, Xavier Darzacq (2017) CTCF and cohesin regulate chromatin loop stability with distinct dynamics eLife 6:e25776 https://doi.org/10.7554/eLife.25776 Claudia Cattoglio, Iryna Pustova, Nike Walther, Jaclyn J Ho, Merle Hantsche-Grininger, Carla J Inouye, M Julius Hossain, Gina M Dailey, Jan Ellenberg, Xavier Darzacq, Robert Tjian, Anders S Hansen (2019) Determining cellular CTCF and cohesin abundances to constrain 3D genome models eLife 8:e40164 https://doi.org/10.7554/eLife.40164 Goel, V.Y., Huseyin, M.K. & Hansen, A.S. Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments. Nat Genet 55, 1048–1056 (2023). https://doi.org/10.1038/s41588-023-01391-1 Related Episodes Biophysical Modeling of 3-D Genome Organization (Leonid Mirny) Unraveling Mechanisms of Chromosome Formation (Job Dekker) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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