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Epigenetics Podcast

Epigenetics Podcast

By: Active Motif
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 Discover the stories behind the science!Copyright 2020. All rights reserved. Biological Sciences Science
Episodes
  • RNA modifications and Gene Expression (Michaela Frye)

    RNA modifications and Gene Expression (Michaela Frye)
    Mar 26 2026

    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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    45 mins
  • Polycomb and Three-Dimensional Genome Organisation (Oliver Bell)

    Polycomb and Three-Dimensional Genome Organisation (Oliver Bell)
    Mar 12 2026
    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.7601926Hathaway, 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.2012.03.052Moussa, 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/s41467-019-09628-6Yelagandula, 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/s41556-022-01051-2Bsteh, 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 MastodonEpigenetics Podcast on BlueskyDr. Stefan Dillinger on LinkedInActive Motif on LinkedInActive Motif on BlueskyEmail: podcast@activemotif.com
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    49 mins
  • From Placeholder Nucleosomes to Zygotic Genome Activation (Patrick Murphy)

    From Placeholder Nucleosomes to Zygotic Genome Activation (Patrick Murphy)
    Feb 26 2026

    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
    Show More Show Less
    39 mins
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