Epigenetics Podcast

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Evolutionary Epigenetic Clocks and Epigenetic Inheritance in Plants (Frank Johannes)
In this episode of the Epigenetics Podcast, we talked with Dr. Frank Johannes from the Technical University of Munich in Freising about his work on evolutionary clocks and epigenetic inheritance in plants. In this episode we discuss Dr. Johannes pursuits in understanding how heritable epigenetic variations, particularly through DNA methylation, affect phenotypic diversity in plants. He shared insights about groundbreaking research initiatives he has led, including one of the first population epigenetic studies in plants that effectively linked heritable DNA methylation changes to critical traits like flowering time and root length. This work underscored the importance of epigenetic factors that extend beyond traditional genetic sequences, illustrating a significant shift in how we comprehend inheritance and trait variation in organisms. As we dug deeper into the science, we examined Dr. Johannes's innovative approaches to studying chromatin-based mechanisms of genome regulation, allowing for a nuanced understanding of epigenetic inheritance. His lab’s extensive phenotyping of Arabidopsis plants highlighted how inducing heritable variations in DNA methylation could lead to significant trait outcomes – results that have substantial implications for agriculture and understanding complex characteristics across generations. The dialogue continued to unravel the dynamics between forward and backward epimutations, delving into their heritable nature and their rapid accumulation compared to traditional genetic mutations. Dr. Johannes overturned conventional understanding by presenting epigenetic processes that are not as static as once thought, providing compelling evidence that these spontaneous changes could inform evolutionary clocks; a concept that offers new avenues for studying the relationships between species over relatively short timeframes. Moreover, we discussed the exciting concept of epigenetic clocks, which play a role in assessing the age of various species, including trees. The potential applications for such clocks in environmental management and the assessment of tree vitality further illuminated the practical impacts of Dr. Johannes's research. These insights also pave the way for sophisticated non-invasive methods of understanding plant biology, which can revolutionize forest management practices in the face of climate change and other ecological pressures. References Colomé-Tatché M, Cortijo S, Wardenaar R, Morgado L, Lahouze B, Sarazin A, Etcheverry M, Martin A, Feng S, Duvernois-Berthet E, Labadie K, Wincker P, Jacobsen SE, Jansen RC, Colot V, Johannes F. Features of the Arabidopsis recombination landscape resulting from the combined loss of sequence variation and DNA methylation. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16240-5. doi: 10.1073/pnas.1212955109. Epub 2012 Sep 17. PMID: 22988127; PMCID: PMC3479620. Cortijo S, Wardenaar R, Colomé-Tatché M, Gilly A, Etcheverry M, Labadie K, Caillieux E, Hospital F, Aury JM, Wincker P, Roudier F, Jansen RC, Colot V, Johannes F. Mapping the epigenetic basis of complex traits. Science. 2014 Mar 7;343(6175):1145-8. doi: 10.1126/science.1248127. Epub 2014 Feb 6. PMID: 24505129. van der Graaf A, Wardenaar R, Neumann DA, Taudt A, Shaw RG, Jansen RC, Schmitz RJ, Colomé-Tatché M, Johannes F. Rate, spectrum, and evolutionary dynamics of spontaneous epimutations. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6676-81. doi: 10.1073/pnas.1424254112. Epub 2015 May 11. PMID: 25964364; PMCID: PMC4450394. Yao N, Zhang Z, Yu L, Hazarika R, Yu C, Jang H, Smith LM, Ton J, Liu L, Stachowicz JJ, Reusch TBH, Schmitz RJ, Johannes F. An evolutionary epigenetic clock in plants. Science. 2023 Sep 29;381(6665):1440-1445. doi: 10.1126/science.adh9443. Epub 2023 Sep 28. PMID: 37769069. Related Episodes Transgenerational Inheritance and Epigenetic Imprinting in Plants (Mary Gehring) Epigenetic Clocks and Biomarkers of Ageing (Morgan Levine) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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Neuroepigenetic Mechanisms and Primate Epigenome Evolution (Boyan Bonev)
In this episode of the Epigenetics Podcast, we talked with Boyan Bonev from the HelmholtzZetrum in Munich about his work on neuroepigenetics, focusing on gene regulation, chromatin architecture, and primate epigenome evolution, This Episode focuses on Dr. Bonev’s recent research, particularly focusing on how chromatin architecture and gene regulation influence neural cell identity and function. He discusses his work investigating transcriptional activity in relation to chromatin insulation, highlighting a critical finding that induced expression of genes does not necessarily lead to chromatin insulation—a point that complicates prior assumptions about the relationship between gene expression and chromatin organization. This study aimed to determine the causal versus correlative aspects of chromatin architecture in brain development and links it to developmental processes and neurodevelopmental disorders. Building on his findings in gene regulation, Dr. Bonev elaborates on a significant study he conducted in his own lab, where he mapped the regulatory landscape of neural differentiation in the mouse neocortex. Here, he employed cutting-edge single-cell sequencing methodologies to analyze intricate gene and enhancer interactions, revealing that selective enhancer-promoter interactions are primarily cell-type specific. This nuanced understanding aids in deciphering the complexities associated with gene expression as it relates to neural stem cells and differentiated neurons, emphasizing the importance of single-cell analyses over bulk sequencing methods. Moreover, Dr. Bonev reveals a novel methodology developed in his lab that allows for the simultaneous assessment of spatial genome organization, chromatin accessibility, and DNA methylation at high resolution. This advancement not only reduces costs but also enhances the potential to correlate higher-dimensional genomic data with specific biological questions, fostering a more integrative approach to understanding genetic regulation. The discussion then shifts focus towards Dr. Bonev's recent project profiling primate epigenome evolution, where he investigated the 3D genome organization, chromatin accessibility, and gene expression among iPSCs and neural stem cells from various species, including humans, chimpanzees, gorillas, and macaques. In this research, he identifies trends related to transcription factor evolution and chromatin modifications across species. The insights gleaned from this work underscore the evolutionary significance of structural variations in the 3D genome, pointing to a possible link between chromatin dynamics and the evolutionary development of the primate brain. References Bonev B, Mendelson Cohen N, Szabo Q, Fritsch L, Papadopoulos GL, Lubling Y, Xu X, Lv X, Hugnot JP, Tanay A, Cavalli G. Multiscale 3D Genome Rewiring during Mouse Neural Development. Cell. 2017 Oct 19;171(3):557-572.e24. doi: https://doi.org/10.1016/j.cell.2017.09.043. PMID: 29053968; PMCID: PMC5651218. Noack, F., Vangelisti, S., Raffl, G. et al. Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler. Nat Neurosci 25, 154–167 (2022). https://doi.org/10.1038/s41593-021-01002-4 Noack F, Vangelisti S, Ditzer N, Chong F, Albert M, Bonev B. Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids. Nat Cell Biol. 2023 Dec;25(12):1873-1883. doi: 10.1038/s41556-023-01296-5. Epub 2023 Nov 23. PMID: 37996647; PMCID: PMC10709149. Related Episodes Characterization of Epigenetic States in the Oligodendrocyte Lineage (Gonçalo Castelo-Branco) Polycomb Proteins, Gene Regulation, and Genome Organization in Drosophila (Giacomo Cavalli) The Effect of lncRNAs on Chromatin and Gene Regulation (John Rinn) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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The Role of H3K4me3 in Embryonic Development (Eva Hörmanseder)
In this episode of the Epigenetics Podcast, we talked with Dr. Eva Hörmanseder from the HelmholtzZentrum in Munich about her work on epigenetic mechanisms in cellular memory and gene regulation. In this episode, we delve into the fascinating world of cellular memory and gene regulation with Dr. Eva Hermanns-Eder from the Helmholtz Zentrum in Munich. Her research centers on how cells maintain their identity through the process of mitotic divisions, which is crucial for understanding both development and various diseases. We explore the role of chromatin dynamics and epigenetic modifications in switching genes on and off over time, which has significant implications for fields like cancer biology and regenerative medicine. The discussion starts with Dr. Hörmanseder's recent studies on epigenetic memories, particularly focusing on the concept of transcriptional memory in nuclear transfer embryos. She explains her work with H3K4 trimethylation, a crucial epigenetic mark associated with active transcription states, detailing experiments that demonstrate the significance of this mark in the context of gene expression during reprogramming. She elaborates on her findings regarding how active genes can remain in a state of transcriptional memory and the implications of such persistence for cellular identity. We also dive into Dr. Hörmanseder's exploration of how transcription factors and chromatin modifications shape the differentiation success of reprogrammed cells. Through her research, she uncovers that different cell types exhibit varying degrees of plasticity and memory retention, which can lead to disparities in successful differentiation. Her innovative use of single-cell sequencing technology reveals surprising insights into the dynamics of cellular reprogramming, especially when comparing reprogrammed cells to their fertilized counterparts. References Hörmanseder E, Simeone A, Allen GE, Bradshaw CR, Figlmüller M, Gurdon J, Jullien J. H3K4 Methylation-Dependent Memory of Somatic Cell Identity Inhibits Reprogramming and Development of Nuclear Transfer Embryos. Cell Stem Cell. 2017 Jul 6;21(1):135-143.e6. doi: 10.1016/j.stem.2017.03.003. Epub 2017 Mar 30. PMID: 28366589; PMCID: PMC5505866. Zikmund, T., Fiorentino, J., Penfold, C., Stock, M., Shpudeiko, P., Agarwal, G., Langfeld, L., Petrova, K., Peshkin, L., Hamperl, S., Scialdone, A., & Hoermanseder, E. (2025). Differentiation success of reprogrammed cells is heterogeneous in vivo and modulated by somatic cell identity memory. Stem Cell Reports, 102447. https://doi.org/10.1016/j.stemcr.2025.102447 Related Episodes H3K4me3, SET Proteins, Isw1, and their Role in Transcription (Jane Mellor) DNA Replication, Transcription and R-loops (Stephan Hamperl) Inheritance of Transcriptional Memory by Mitotic Bookmarking (Sheila Teves) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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Using RICC-Seq to Probe Short Range Chromatin Folding (Viviana Risca)
In this episode of the Epigenetics Podcast, we talked with Viviana Risca from Rockefeller University about her work on RICC-Seq and how it's used to probe DNA-DNA contacts in intact or fixed cells using ionizing radiation. This Interview covers Dr. Viviana Risca's cutting-edge methodologies, such as RICC-seq, which enables high-resolution analysis of chromatin structures without traditional cross-linking biases. We engage in a detailed discussion about how different techniques, such as RICC-seq and Micro-C, complement each other to provide robust insights into nucleosome interactions and chromatin dynamics. Dr. Risca articulates the challenges and innovations within her lab as it navigates through the complexities of chromatin mapping. The episode takes an exciting turn toward traversing the landscape of her future research directions, particularly studying the role of linker histones and other chromatin architectural proteins in regulating gene expression. Dr. Risca emphasizes the importance of understanding chromatin's mechanical properties and how these influence cellular processes like transcriptional regulation, DNA replication, and cellular responses to damage. We also explore her collaborative work that bridges the gap between basic research and clinical applications, particularly in cancer therapy. Dr. Risca shares insights into her investigations into how chromatin dynamics change during cell cycle arrest and their implications for cancer therapy resistance. Our discussion culminates in her reflections on the definition of epigenetics, framing it as the exploration of how cellular mechanisms encode and process information. References Risca VI, Denny SK, Straight AF, Greenleaf WJ. Variable chromatin structure revealed by in situ spatially correlated DNA cleavage mapping. Nature. 2017 Jan 12;541(7636):237-241. doi: 10.1038/nature20781. Epub 2016 Dec 26. PMID: 28024297; PMCID: PMC5526328. Soroczynski J, Anderson LJ, Yeung JL, Rendleman JM, Oren DA, Konishi HA, Risca VI. OpenTn5: Open-Source Resource for Robust and Scalable Tn5 Transposase Purification and Characterization. bioRxiv [Preprint]. 2024 Jul 13:2024.07.11.602973. doi: 10.1101/2024.07.11.602973. PMID: 39026714; PMCID: PMC11257509. Prescott, N. A., Biaco, T., Mansisidor, A., Bram, Y., Rendleman, J., Faulkner, S. C., Lemmon, A. A., Lim, C., Tiersky, R., Salataj, E., Garcia-Martinez, L., Borges, R. L., Morey, L., Hamard, P.-J., Koche, R. P., Risca, V. I., Schwartz, R. E., & David, Y. (2025). A nucleosome switch primes hepatitis B virus infection. Cell, S0092867425001023. https://doi.org/10.1016/j.cell.2025.01.033 Related Episodes Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden) Split-Pool Recognition of Interactions by Tag Extension (SPRITE) (Mitch Guttman) Effects of Non-Enzymatic Covalent Histone Modifications on Chromatin (Yael David) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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The Mechanism of ATP-dependent Remodelers and HP1 Gene Silencing (Geeta Narlikar)
In this episode of the Epigenetics Podcast, we talked with Geeta Narlikar from UCSF about her work on chromatin remodeling, Heterochromatin Protein 1, and the molecular mechanisms that influence the genome. The conversation starts with a pivotal paper from the early days of Dr. Narlikars research career, titled "Distinct Strategies to Make Nucleosomal DNA Accessible," focused on two ATP-dependent remodelers, BRG1 and SNF2H. Here, she notes that while both enzymes operate similarly, they generate different outputs and play distinct biological roles within the cell. The research revealed that BRG1 is more aggressive in altering nucleosome configuration, aligning with its role in transcription activation, while SNF2H showed a more refined approach in the formation of heterochromatin. Transitioning to her work at UCSF, she emphasized the importance of collaboration and mentoring within a research group. Her focus then shifted towards the ACF ATP-dependent chromatin assembly factor, hypothesizing how ACF measures nucleosome distance—an inquiry that led to exciting insights regarding dynamic enzyme behavior. This includes findings that ACF operates not through a static ruler mechanism but rather through a kinetic mechanism, thus continuously adjusting nucleosome positioning based on DNA length during chromatin assembly. Dr. Narlikar also delved into her studies on heterochromatin protein 1 (HP1), highlighting how HP1 recognizes methylation marks and assembles on chromatin to facilitate gene silencing. This segment of the discussion underscored her shift to studying phase separation and its implications in the organization of chromatin. Notably, her lab made significant advancements in understanding how HP1 forms phase-separated droplets, a finding that was independently corroborated by other laboratories, demonstrating the utility of collaborative scientific inquiry. In discussing the nuances of chromatin dynamics, Dr. Narlikar also introduced her investigations into the INO80 complex, detailing its distinct mechanism for nucleosome movement compared to other remodelers. Each remodeling complex, as she elucidated, has unique catalytic capabilities while still utilizing similar biochemical foundations, highlighting the diverse regulatory roles these proteins play within cells. References Racki LR, Yang JG, Naber N, Partensky PD, Acevedo A, Purcell TJ, Cooke R, Cheng Y, Narlikar GJ. The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes. Nature. 2009 Dec 24;462(7276):1016-21. doi: 10.1038/nature08621. PMID: 20033039; PMCID: PMC2869534. Canzio D, Liao M, Naber N, Pate E, Larson A, Wu S, Marina DB, Garcia JF, Madhani HD, Cooke R, Schuck P, Cheng Y, Narlikar GJ. A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly. Nature. 2013 Apr 18;496(7445):377-81. doi: 10.1038/nature12032. Epub 2013 Mar 13. PMID: 23485968; PMCID: PMC3907283. Sinha KK, Gross JD, Narlikar GJ. Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler. Science. 2017 Jan 20;355(6322):eaaa3761. doi: 10.1126/science.aaa3761. PMID: 28104838; PMCID: PMC5656449. Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB, Burlingame AL, Agard DA, Redding S, Narlikar GJ. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature. 2017 Jul 13;547(7662):236-240. doi: 10.1038/nature22822. Epub 2017 Jun 21. PMID: 28636604; PMCID: PMC5606208. Sanulli S, Trnka MJ, Dharmarajan V, Tibble RW, Pascal BD, Burlingame AL, Griffin PR, Gross JD, Narlikar GJ. HP1 reshapes nucleosome core to promote phase separation of heterochromatin. Nature. 2019 Nov;575(7782):390-394. doi: 10.1038/s41586-019-1669-2. Epub 2019 Oct 16. PMID: 31618757; PMCID: PMC7039410. Related Episodes Enhancers and Chromatin Remodeling in Mammary Gland Development (Camila dos Santos) Heterochromatin Protein 1 and its Influence on the Structure of Chromatin (Serena Sanulli) Heterochromatin and Phase Separation (Gary Karpen) Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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