Long-Range Transcriptional Control by 3D Chromosome Structure (Luca Giorgetti)

In this episode Dr. Raffaele Teperino shares insights from his ongoing research focused on developmental programming, particularly how paternal health before conception influences not only offspring health but also maternal health outcomes. As we trace his academic journey from studying biotechnology and pharmacology to leading his own lab, Dr. Teperino reflects on his early fascination with medicine, the pivotal experiences that shaped his career, and the integration of epigenetics into understanding metabolic diseases. We discuss the nuances of epigenetics—going beyond simple chromatin biology to examine its wider implications on phenotypic variation. Dr. Teperino emphasizes his approach of modeling relevant physiological phenomena in the lab to better understand the underlying mechanisms driving conditions like obesity and metabolic disruption. A particular focus is placed on his experiences during his postdoctoral years, where he investigated the developmental pathways of hedgehog signaling and its metabolic implications in adipogenesis. Our talk shifts towards the practical implications of his research, highlighting recent investigations into how circadian rhythms and paternal lifestyles influence offspring health. Dr. Teperino reveals his findings on how disturbances in circadian rhythms can lead to intergenerational health issues, showcasing the surprising effects observed in offspring of fathers experiencing circadian misalignment. We delve into the significance of seminal fluid as a potential medium for intergenerational transfer of stress responses, examining the role of stress hormones and their impacts on fetal development. As we explore a fascinating recent study highlighting the impact of paternal diets on future generations, Dr. Teperino underscores the importance of understanding the shorter exposure periods sufficient to trigger these health changes. He presents data that links paternal obesity and preconception health to an increased risk of obesity and insulin resistance in children, challenging traditional narratives around maternal responsibility for offspring health.   References Darr J, Tomar A, Lassi M, Gerlini R, Berti L, Hering A, Scheid F, Hrabě de Angelis M, Witting M, Teperino R. iTAG-RNA Isolates Cell-Specific Transcriptional Responses to Environmental Stimuli and Identifies an RNA-Based Endocrine Axis. Cell Rep. 2020 Mar 3;30(9):3183-3194.e4. doi: 10.1016/j.celrep.2020.02.020. PMID: 32130917. Lassi M, Tomar A, Comas-Armangué G, Vogtmann R, Dijkstra DJ, Corujo D, Gerlini R, Darr J, Scheid F, Rozman J, Aguilar-Pimentel A, Koren O, Buschbeck M, Fuchs H, Marschall S, Gailus-Durner V, Hrabe de Angelis M, Plösch T, Gellhaus A, Teperino R. Disruption of paternal circadian rhythm affects metabolic health in male offspring via nongerm cell factors. Sci Adv. 2021 May 26;7(22):eabg6424. doi: 10.1126/sciadv.abg6424. PMID: 34039610; PMCID: PMC8153725. Tomar A, Gomez-Velazquez M, Gerlini R, Comas-Armangué G, Makharadze L, Kolbe T, Boersma A, Dahlhoff M, Burgstaller JP, Lassi M, Darr J, Toppari J, Virtanen H, Kühnapfel A, Scholz M, Landgraf K, Kiess W, Vogel M, Gailus-Durner V, Fuchs H, Marschall S, Hrabě de Angelis M, Kotaja N, Körner A, Teperino R. Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs. Nature. 2024 Jun;630(8017):720-727. doi: 10.1038/s41586-024-07472-3. Epub 2024 Jun 5. PMID: 38839949; PMCID: PMC11186758.   Related Episodes The Impact of Paternal Diet on Offspring Metabolism (Upasna Sharma) Transgenerational Inheritance and Evolution of Epimutations (Peter Sarkies) 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: [email protected]

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]

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]

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]  

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]

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]

In this episode of the Epigenetics Podcast, we talked with Giacomo Cavalli from the Institute of Human Genetics in Montpellier about his work on critical aspects of epigenetic regulation, particularly the role of Polycomb proteins and chromatin architecture. We start the Interview by talking about Dr. Cavalli's work on Polycomb function in maintaining chromatin states and how it relates to gene regulation. He shares insights from his early lab experiences, where he aimed to understand the inheritance mechanisms of chromatin states through various models, including the FAB7 cellular memory module. The discussion uncovers how Polycomb proteins can silence gene expression and the complex interplay between different epigenetic factors that govern this process. Dr. Cavalli also addresses how he has investigated the recruitment mechanisms of Polycomb complexes, highlighting the roles of several DNA-binding proteins, including DSP-1 and GAGA factor, in this intricate regulatory landscape. He emphasizes the evolution of our understanding of Polycomb recruitment, illustrating the multifactorial nature of this biological puzzle. As the conversation progresses, we explore Dr. Cavalli's fascinating research into the three-dimensional organization of the genome. He explains his contributions to mapping chromosomal interactions within Drosophila and the distinctions observed when performing similar studies in mammalian systems. Key findings regarding topologically associated domains (TADs) and their association with gene expression are presented, alongside the implications for our understanding of gene regulation in development and disease.   References Déjardin, J., Rappailles, A., Cuvier, O., Grimaud, C., Decoville, M., Locker, D., & Cavalli, G. (2005). Recruitment of Drosophila Polycomb group proteins to chromatin by DSP1. Nature, 434(7032), 533–538. https://doi.org/10.1038/nature03386 Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., & Cavalli, G. (2012). Three-dimensional folding and functional organization principles of the Drosophila genome. Cell, 148(3), 458–472. https://doi.org/10.1016/j.cell.2012.01.010 Bonev, B., Mendelson Cohen, N., Szabo, Q., Fritsch, L., Papadopoulos, G. L., Lubling, Y., Xu, X., Lv, X., Hugnot, J. P., Tanay, A., & Cavalli, G. (2017). Multiscale 3D Genome Rewiring during Mouse Neural Development. Cell, 171(3), 557–572.e24. https://doi.org/10.1016/j.cell.2017.09.043 Szabo, Q., Donjon, A., Jerković, I., Papadopoulos, G. L., Cheutin, T., Bonev, B., Nora, E. P., Bruneau, B. G., Bantignies, F., & Cavalli, G. (2020). Regulation of single-cell genome organization into TADs and chromatin nanodomains. Nature genetics, 52(11), 1151–1157. https://doi.org/10.1038/s41588-020-00716-8   Related Episodes BET Proteins and Their Role in Chromosome Folding and Compartmentalization (Kyle Eagen) Long-Range Transcriptional Control by 3D Chromosome Structure (Luca Giorgetti) Epigenetic Landscapes During Cancer (Luciano Di Croce)   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]

In this episode of the Epigenetics Podcast, we talked with Ferdinand von Meyenn from ETH Zürich about his work on the interplay of nutrition, metabolic pathways, and epigenetic regulation. To start Dr. Meyenn recounts his pivotal research on DNA methylation in naive embryonic stem cells during his time with Wolf Reick. He explains the dynamics of global demethylation in naive stem cells, revealing the key enzymes involved and the unexpected findings surrounding UHF1—its role in maintaining DNA methylation levels and influencing the methylation landscape during early embryonic development. Dr. Meyenn then shares his perspective on the scientific transition to establishing his own lab at ETH. He reflects on his ambitions to merge the fields of metabolism and epigenetics, which is a recurring theme throughout his research. By investigating the interplay between metabolic changes and epigenetic regulation, he aims to uncover how environmental factors affect cellular dynamics across various tissues. This leads to a discussion of his recent findings on histone lactylation and its implications in cellular metabolism, as well as the intricacies of epigenetic imprinting in stem cell biology. Last but not least we touch upon Dr. Meyenn’s most recent study, published in Nature, investigating the epigenetic effects of obesity. He provides a detailed overview of how adipose tissue undergoes transcriptional and epigenetic rearrangements during weight fluctuations. The conversation highlights the notion of epigenetic memory in adipocytes, showing how obesity is not just a temporary state but leaves lasting cellular changes that can predispose individuals to future weight regain after dieting. This exploration opens avenues for potential therapeutic interventions aimed at reversing adverse epigenetic modifications.   References von Meyenn, F., Iurlaro, M., Habibi, E., Liu, N. Q., Salehzadeh-Yazdi, A., Santos, F., Petrini, E., Milagre, I., Yu, M., Xie, Z., Kroeze, L. I., Nesterova, T. B., Jansen, J. H., Xie, H., He, C., Reik, W., & Stunnenberg, H. G. (2016). Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells. Molecular cell, 62(6), 848–861. https://doi.org/10.1016/j.molcel.2016.04.025 Galle, E., Wong, C. W., Ghosh, A., Desgeorges, T., Melrose, K., Hinte, L. C., Castellano-Castillo, D., Engl, M., de Sousa, J. A., Ruiz-Ojeda, F. J., De Bock, K., Ruiz, J. R., & von Meyenn, F. (2022). H3K18 lactylation marks tissue-specific active enhancers. Genome biology, 23(1), 207. https://doi.org/10.1186/s13059-022-02775-y Agostinho de Sousa, J., Wong, C. W., Dunkel, I., Owens, T., Voigt, P., Hodgson, A., Baker, D., Schulz, E. G., Reik, W., Smith, A., Rostovskaya, M., & von Meyenn, F. (2023). Epigenetic dynamics during capacitation of naïve human pluripotent stem cells. Science advances, 9(39), eadg1936. https://doi.org/10.1126/sciadv.adg1936 Bonder, M. J., Clark, S. J., Krueger, F., Luo, S., Agostinho de Sousa, J., Hashtroud, A. M., Stubbs, T. M., Stark, A. K., Rulands, S., Stegle, O., Reik, W., & von Meyenn, F. (2024). scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood. Nature communications, 15(1), 7567. https://doi.org/10.1038/s41467-024-51833-5 Hinte, L. C., Castellano-Castillo, D., Ghosh, A., Melrose, K., Gasser, E., Noé, F., Massier, L., Dong, H., Sun, W., Hoffmann, A., Wolfrum, C., Rydén, M., Mejhert, N., Blüher, M., & von Meyenn, F. (2024). Adipose tissue retains an epigenetic memory of obesity after weight loss. Nature, 636(8042), 457–465. https://doi.org/10.1038/s41586-024-08165-7   Related Episodes Nutriepigenetics: The Effects of Diet on Behavior (Monica Dus) Epigenetic and Metabolic Regulation of Early Development (Jan Żylicz) Effects of Environmental Cues on the Epigenome and Longevity (Paul Shiels)   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]

In this episode of the Epigenetics Podcast, we talked with Vijay Ramani from the Gladstone Institute about his work on Single-Molecule Adenine Methylated Oligonucleosome Sequencing Assay (SAMOSA). Our discussion starts with Vijay Ramani's impactful contributions to the field during his time in Jay Shendure's lab, where he worked on several innovative methods, including RNA proximity ligation. This project was conceived during his graduate studies, aiming to adapt techniques from DNA research to investigate RNA structures—a largely unexplored area at the time. We delved into the nuances of his experiences in graduate school, emphasizing how critical it was to have mentors who provided room for creativity and autonomy in experimental design. Dr. Ramani then shares insights about his foray into developing more refined methodologies, such as in-situ DNA Hi-C, a revolutionary protocol tailored for three-dimensional genomic mapping. He explained the rationale behind his projects, comparing the outcomes with contemporaneous advancements in methods like Micro-C. The discussion highlighted the importance of understanding enzyme bias in chromatin studies and the need for meticulous experimental design to ensure the validity of biological interpretations. We further explored exciting advancements in single-cell genomics, specifically Ramani's work on developing sci-Hi-C. This innovative technique leverages combinatorial indexing to allow high-resolution mapping of chromatin architecture at the single-cell level, a significant leap forward in understanding the complexities of gene regulation. As we progress, Ramani detailed his transition from graduate student to independent investigator starting his own lab. He elaborated on the challenges and excitements associated with establishing his research focus in chromatin structure and function using advanced sequencing technologies. Employing various strategies, including the innovative SAMOSA assay, his research seeks to elucidate the mechanisms by which chromatin structure influences transcriptional regulation. We also discussed the heterogeneity of chromatin and its implications for gene expression. Ramani provided a fascinating perspective on how variations in chromatin structure could affect gene activity, highlighting potential avenues for future research that aims to untangle the complex dynamics at play in both healthy and diseased states.   References Ramani, V., Cusanovich, D., Hause, R. et al. Mapping 3D genome architecture through in situ DNase Hi-C. Nat Protoc 11, 2104–2121 (2016). https://doi.org/10.1038/nprot.2016.126 Nour J Abdulhay, Colin P McNally, Laura J Hsieh, Sivakanthan Kasinathan, Aidan Keith, Laurel S Estes, Mehran Karimzadeh, Jason G Underwood, Hani Goodarzi, Geeta J Narlikar, Vijay Ramani (2020) Massively multiplex single-molecule oligonucleosome footprinting eLife 9:e59404. https://doi.org/10.7554/eLife.59404 Abdulhay, N.J., Hsieh, L.J., McNally, C.P. et al. Nucleosome density shapes kilobase-scale regulation by a mammalian chromatin remodeler. Nat Struct Mol Biol 30, 1571–1581 (2023). https://doi.org/10.1038/s41594-023-01093-6 Nanda, A.S., Wu, K., Irkliyenko, I. et al. Direct transposition of native DNA for sensitive multimodal single-molecule sequencing. Nat Genet 56, 1300–1309 (2024). https://doi.org/10.1038/s41588-024-01748-0   Related Episodes Epigenetic Mechanisms in Genome Regulation and Developmental Programming (James Hackett) Chromatin Profiling: From ChIP to CUT&RUN, CUT&Tag and CUTAC (Steven Henikoff) Split-Pool Recognition of Interactions by Tag Extension (SPRITE) (Mitch Guttman)   Contact Epigenetics Podcast on X Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Epigenetics Podcast on Threads Active Motif on X Active Motif on LinkedIn Email: [email protected]

In this episode of the Epigenetics Podcast, we talked with Maxim Greenberg from the Institute Jacob Monot about his work on epigenetic consequences of DNA methylation in development. In this interview we explore how Dr. Greenberg’s work at UCLA involved pioneering experiments on DNA methylation mechanisms and how this period was marked by significant collaborative efforts within a highly competitive yet supportive lab environment that ultimately lead to publications in high impact journals. His transition to a postdoctoral position at the Institut Curie with Deborah Bourc'his harnessed his expertise in mammalian systems, examining chromatin changes and the implications for embryonic development. Dr. Greenberg explained the nuances of his research, particularly how chromatin modifications during early development can influence gene regulatory mechanisms later in life, providing a compelling narrative about the potential long-term impacts of epigenetic changes that occur in utero. Throughout our conversation, we examined the intricate relationship between DNA methylation and Polycomb repression, discussing how these epigenetic mechanisms interact and the functional outcomes of their regulation. Dr. Greenberg's insights into his recent studies reveal a commitment to unraveling the complexities of enhancer-promoter interactions in the context of epigenetic regulation.   References Greenberg, M. V., Ausin, I., Chan, S. W., Cokus, S. J., Cuperus, J. T., Feng, S., Law, J. A., Chu, C., Pellegrini, M., Carrington, J. C., & Jacobsen, S. E. (2011). Identification of genes required for de novo DNA methylation in Arabidopsis. Epigenetics, 6(3), 344–354. https://doi.org/10.4161/epi.6.3.14242 Greenberg, M. V., Glaser, J., Borsos, M., Marjou, F. E., Walter, M., Teissandier, A., & Bourc'his, D. (2017). Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth. Nature genetics, 49(1), 110–118. https://doi.org/10.1038/ng.3718 Greenberg, M., Teissandier, A., Walter, M., Noordermeer, D., & Bourc'his, D. (2019). Dynamic enhancer partitioning instructs activation of a growth-related gene during exit from naïve pluripotency. eLife, 8, e44057. https://doi.org/10.7554/eLife.44057 Monteagudo-Sánchez, A., Richard Albert, J., Scarpa, M., Noordermeer, D., & Greenberg, M. V. C. (2024). The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation. Nucleic acids research, 52(18), 10934–10950. https://doi.org/10.1093/nar/gkae724 Richard Albert, J., Urli, T., Monteagudo-Sánchez, A., Le Breton, A., Sultanova, A., David, A., Scarpa, M., Schulz, M., & Greenberg, M. V. C. (2024). DNA methylation shapes the Polycomb landscape during the exit from naive pluripotency. Nature structural & molecular biology, 10.1038/s41594-024-01405-4. Advance online publication. https://doi.org/10.1038/s41594-024-01405-4   Related Episodes DNA Methylation and Mammalian Development (Déborah Bourc'his) Circulating Epigenetic Biomarkers in Cancer (Charlotte Proudhon) Epigenetic Mechanisms in Genome Regulation and Developmental Programming (James Hackett)   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]