Epigenetics Podcast

Epigenetics and Epitranscriptomics in Cancer (Manel Esteller)

In this episode of the Epigenetics Podcast, we caught up with Manel Esteller, Director of the Josep Carreras Leukemia Research Institute to talk about his work on Epigenetics and Epitranscriptomics in Cancer.
The focus of Manel Esteller's research career and the focus of his current team is to characterize the epigenome and epitranscriptome of cancer cells in comparison to healthy cells, and their interplay. Ultimately, their goal is to use this knowledge to develop new therapies for cancer. Key achievements from the Esteller lab began with the discovery of the first miRNA that undergoes specific cancer-methylation associated silencing. The team further identified many more miRNAs that also play a role in cancer. Next to miRNAs, Manel Esteller studied the influence of lncRNAs, enhancers and DNA methylation on cancer development and progression, insights that may be used to develop cancer biomarkers and potential treatments.  
 
References
Guil, S., Soler, M., Portela, A., Carrère, J., Fonalleras, E., Gómez, A., Villanueva, A., & Esteller, M. (2012). Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nature Structural & Molecular Biology, 19(7), 664–670. https://doi.org/10.1038/nsmb.2315
Vizoso, M., Ferreira, H. J., Lopez-Serra, P., Carmona, F. J., Martínez-Cardús, A., Girotti, M. R., Villanueva, A., Guil, S., Moutinho, C., Liz, J., Portela, A., Heyn, H., Moran, S., Vidal, A., Martinez-Iniesta, M., Manzano, J. L., Fernandez-Figueras, M. T., Elez, E., Muñoz-Couselo, E., … Esteller, M. (2015). Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. Nature Medicine, 21(7), 741–750. https://doi.org/10.1038/nm.3863
Agrelo, R., Cheng, W.-H., Setien, F., Ropero, S., Espada, J., Fraga, M. F., Herranz, M., Paz, M. F., Sanchez-Cespedes, M., Artiga, M. J., Guerrero, D., Castells, A., von Kobbe, C., Bohr, V. A., & Esteller, M. (2006). Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proceedings of the National Academy of Sciences of the United States of America, 103(23), 8822–8827. https://doi.org/10.1073/pnas.0600645103
Lopez-Serra, P., Marcilla, M., Villanueva, A., Ramos-Fernandez, A., Palau, A., Leal, L., Wahi, J. E., Setien-Baranda, F., Szczesna, K., Moutinho, C., Martinez-Cardus, A., Heyn, H., Sandoval, J., Puertas, S., Vidal, A., Sanjuan, X., Martinez-Balibrea, E., Viñals, F., Perales, J. C., … Esteller, M. (2014). A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect. Nature Communications, 5, 3608. https://doi.org/10.1038/ncomms4608
Rosselló-Tortella, M., Llinàs-Arias, P., Sakaguchi, Y., Miyauchi, K., Davalos, V., Setien, F., Calleja-Cervantes, M. E., Piñeyro, D., Martínez-Gómez, J., Guil, S., Joshi, R., Villanueva, A., Suzuki, T., & Esteller, M. (2020). Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer. Proceedings of the National Academy of Sciences of the United States of America, 117(34), 20785–20793. https://doi.org/10.1073/pnas.2003358117
Castro de Moura, M., Davalos, V., Planas-Serra, L., Alvarez-Errico, D., Arribas, C., Ruiz, M., Aguilera-Albesa, S., Troya, J., Valencia-Ramos, J., Vélez-Santamaria, V., Rodríguez-Palmero, A., Villar-Garcia, J., Horcajada, J. P., Albu, S., Casasnovas, C., Rull, A., Reverte, L., Dietl, B., Dalmau, D., … Esteller, M. (2021). Epigenome-wide association study of COVID-19 severity with respiratory failure. EBioMedicine, 66, 103339. https://doi.org/10.1016/j.ebiom.2021.103339
 
Related Episodes
CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird)
Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard)
Cancer and Epigenetics (David Jones)
 
Contact
Active Motif on Twitter
Epigenetics Podcast on Twitter
Active Motif on LinkedIn
Active Motif on Facebook
Email: podcast@activemotif.com

Enhancer-Promoter Interactions During Development (Yad Ghavi-Helm)

In this episode of the Epigenetics Podcast, we caught up with Yad Ghavi-Helm from the Institut de Génomique Functionnelle de Lyon to talk about her work on enhancer-promoter interactions during development.
The Laboratory of Yad Ghavi-Helm focuses on how developmental genes are regulated by enhancers. Their work shows that developmental genes are often regulated by more than one enhancer and that those enhancers can often be located many kilobases away on the linear chromosome. Furthermore, their research also indicates that the interactions between promoters and their respective enhancers are usually established before the expression of the target gene is switched on, and that those interactions are generally stable during embryogenesis. In addition, those stable interactions seem to coincide with paused RNA Pol II being located at those promoters before gene activation.
References
Ghavi-Helm, Y., Michaut, M., Acker, J., Aude, J.-C., Thuriaux, P., Werner, M., & Soutourina, J. (2008). Genome-wide location analysis reveals a role of TFIIS in RNA polymerase III transcription. Genes & Development, 22(14), 1934–1947. https://doi.org/10.1101/gad.471908
Ghavi-Helm, Y., Klein, F. A., Pakozdi, T., Ciglar, L., Noordermeer, D., Huber, W., & Furlong, E. E. M. (2014). Enhancer loops appear stable during development and are associated with paused polymerase. Nature, 512(7512), 96–100. https://doi.org/10.1038/nature13417
Ghavi-Helm, Y., Jankowski, A., Meiers, S., Viales, R. R., Korbel, J. O., & Furlong, E. E. M. (2019). Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression. Nature Genetics, 51(8), 1272–1282. https://doi.org/10.1038/s41588-019-0462-3
 
Related Episodes
Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)
Unraveling Mechanisms of Chromosome Formation (Job Dekker)
Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)
 
Contact
Active Motif on Twitter
Epigenetics Podcast on Twitter
Active Motif on LinkedIn
Active Motif on Facebook
Email: podcast@activemotif.com

The Effect of Vitamin D on the Epigenome (Folami Ideraabdullah)

In this episode of the Epigenetics Podcast, we caught up with Folami Ideraabdullah from the University of Chapel Hill to talk about her work on the environmental modulation of the epigenome during development.
The lab of Folami Ideraabdullah focuses on studying how environmental factors modulate the epigenome. In particular the team investigates how Vitamin D levels influence epigenetic processes and, hence, the susceptibility for diseases like adipositas. Folami Ideraabdullah started with a genome-wide screen of DNA Methylation patterns that are observed after Vitamin D depletion. This work was then followed up by investigating the impact of Vitamin D depletion on mouse sperm DNA methylation.
 
References
Xue, J., Schoenrock, S. A., Valdar, W., Tarantino, L. M., & Ideraabdullah, F. Y. (2016). Maternal vitamin D depletion alters DNA methylation at imprinted loci in multiple generations. Clinical Epigenetics, 8(1), 107. https://doi.org/10.1186/s13148-016-0276-4
Xue, J., Gharaibeh, R. Z., Pietryk, E. W., Brouwer, C., Tarantino, L. M., Valdar, W., & Ideraabdullah, F. Y. (2018). Impact of vitamin D depletion during development on mouse sperm DNA methylation. Epigenetics, 13(9), 959–974. https://doi.org/10.1080/15592294.2018.1526027
Xue, J., Hutchins, E. K., Elnagheeb, M., Li, Y., Valdar, W., McRitchie, S., Sumner, S., & Ideraabdullah, F. Y. (2020). Maternal Liver Metabolic Response to Chronic Vitamin D Deficiency Is Determined by Mouse Strain Genetic Background. Current Developments in Nutrition, 4(8), nzaa106. https://doi.org/10.1093/cdn/nzaa106
 
Related Episodes
Nutriepigenetics: The Effects of Diet on Behavior (Monica Dus)
Epigenetic Influence on Memory Formation and Inheritance (Isabelle Mansuy)
Epigenetic Origins Of Heterogeneity And Disease (Andrew Pospisilik)
 
Contact
Active Motif on Twitter
Epigenetics Podcast on Twitter
Active Motif on LinkedIn
Active Motif on Facebook
Email: podcast@activemotif.com

H3K4me3, Set-Proteins, Isw1 and their Role in Transcription (Jane Mellor)

In this episode of the Epigenetics Podcast, we caught up with Jane Mellor from the University of Oxford to talk about her work on H3K4me3, SET proteins, Isw1 and their role in transcription.
Since the beginning of the century, Jane Mellor and her team have focused on H3K4 trimethylation and the factors that influence this mark. They discovered that H3K4me3 is an almost universal mark of the first nucleosome in every transcribed unit and all organisms. She could subsequently, together with the Kouzarides lab, identify SetD1, the enzyme that is responsible for writing this modification. Later on, the team characterized Isw1, a chromatin remodeler which “reads” H3K4me3. More recently the lab focuses on how the polymerase transcribes throughout the first nucleosomes of the transcribed region at the +2 nucleosome, with the help of Spt4.
 
References
Santos-Rosa, H., Schneider, R., Bannister, A. J., Sherriff, J., Bernstein, B. E., Emre, N. C. T., Schreiber, S. L., Mellor, J., & Kouzarides, T. (2002). Active genes are tri-methylated at K4 of histone H3. Nature, 419(6905), 407–411. https://doi.org/10.1038/nature01080
Morillon, A., O’Sullivan, J., Azad, A., Proudfoot, N., & Mellor, J. (2003). Regulation of Elongating RNA Polymerase II by Forkhead Transcription Factors in Yeast. Science, 300(5618), 492–495. https://doi.org/10.1126/science.1081379
Morillon, A., Karabetsou, N., O’Sullivan, J., Kent, N., Proudfoot, N., & Mellor, J. (2003). Isw1 Chromatin Remodeling ATPase Coordinates Transcription Elongation and Termination by RNA Polymerase II. Cell, 115(4), 425–435. https://doi.org/10.1016/S0092-8674(03)00880-8
Uzun, Ü., Brown, T., Fischl, H., Angel, A., & Mellor, J. (2021). Spt4 facilitates the movement of RNA polymerase II through the +2 nucleosomal barrier. Cell Reports, 36(13), 109755. https://doi.org/10.1016/j.celrep.2021.109755
 
Related Episodes
Effects of Non-Enzymatic Covalent Histone Modifications on Chromatin (Yael David)
Nutriepigenetics: The Effects of Diet on Behavior (Monica Dus)
Epigenetic Origins Of Heterogeneity And Disease (Andrew Pospisilik)
 
Contact
Active Motif on Twitter
Epigenetics Podcast on Twitter
Active Motif on LinkedIn
Active Motif on Facebook
Email: podcast@activemotif.com

The role of DNA Methylation in Epilepsy (Katja Kobow)

In this episode of the Epigenetics Podcast, we caught up with Katja Kobow from the Universitätsklinikum Erlangen to talk about her work on the role of DNA methylation in Epilepsy.
Katja Kobow started studying the role of Epigenetics in Epilepsy by doing a genome wide Bisulfite-Sequencing screen that revealed a typical DNA methylation signature of epileptic patients versus healthy controls. After these initial results in human patient samples, she switched to an animal model to investigate this further. Now the focus of the Kobow Lab is to look for the same DNA methylation signature in blood samples, using this as a basis for the development of a potential prognostic marker for Epilepsy.
 
References
Jablonski, Janos, Lucas Hoffmann, Ingmar Blümcke, Anna Fejtová, Steffen Uebe, Arif B. Ekici, Vadym Gnatkovsky, and Katja Kobow. 2021. “Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study.” Cells 10(11):3004. doi: 10.3390/cells10113004.
Jablonski, Janos, Lucas Hoffmann, Ingmar Blümcke, Anna Fejtová, Steffen Uebe, Arif B. Ekici, Vadym Gnatkovsky, and Katja Kobow. 2021. “Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study.” Cells 10(11):3004. doi: 10.3390/cells10113004.
Kobow, Katja, Mark Ziemann, Harikrishnan Kaipananickal, Ishant Khurana, Angelika Mühlebner, Martha Feucht, Johannes A. Hainfellner, Thomas Czech, Eleonora Aronica, Tom Pieper, Hans Holthausen, Manfred Kudernatsch, Hajo Hamer, Burkhard S. Kasper, Karl Rössler, Valerio Conti, Renzo Guerrini, Roland Coras, Ingmar Blümcke, Assam El‐Osta, and Antony Kaspi. 2019. “Genomic DNA Methylation Distinguishes Subtypes of Human Focal Cortical Dysplasia.” Epilepsia 60(6):1091–1103. doi: 10.1111/epi.14934.
Dębski, Konrad J., Asla Pitkanen, Noora Puhakka, Anna M. Bot, Ishant Khurana, Kn Harikrishnan, Mark Ziemann, Antony Kaspi, Assam El-Osta, Katarzyna Lukasiuk, and Katja Kobow. 2016. “Etiology Matters – Genomic DNA Methylation Patterns in Three Rat Models of Acquired Epilepsy.” Scientific Reports 6(1):25668. doi: 10.1038/srep25668.
Kobow, Katja, Antony Kaspi, K. N. Harikrishnan, Katharina Kiese, Mark Ziemann, Ishant Khurana, Ina Fritzsche, Jan Hauke, Eric Hahnen, Roland Coras, Angelika Mühlebner, Assam El-Osta, and Ingmar Blümcke. 2013. “Deep Sequencing Reveals Increased DNA Methylation in Chronic Rat Epilepsy.” Acta Neuropathologica 126(5):741–56. doi: 10.1007/s00401-013-1168-8.
 
Related Episodes
CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird)
Effects of DNA Methylation on Chromatin Structure and Transcription (Dirk Schübeler)
Effects of DNA Methylation on Diabetes (Charlotte Ling)
 
Contact
Active Motif on Twitter
Epigenetics Podcast on Twitter
Active Motif on LinkedIn
Active Motif on Facebook
Email: podcast@activemotif.com

MacroH2A Function in Development and Disease (Emily Bernstein)

In this episode of the Epigenetics Podcast, we caught up with Emily Bernstein from Icahn Schoon of Medicine at Mount Sinai to talk about her work on MacroH2A function and the role of Polycomb proteins in its epigenetic regulation, and how this affects in stem cell development and disease.
The Bernstein Lab focuses on histone variants, in particular the H2A variant macroH2A. Chromatin architecture is influenced by the composition of the nucleosome and, hence, exchanging the core histones for histone variants can have a major impact on chromatin structure. MacroH2A variantsare the most unique histone variants due to a 30kDa non-histone domain (macro domain) at their C-termini. This macro domain likely confers important functions to macroH2A variants, which have important regulatory roles in the cell. Among other things, the Bernstein Lab has shown that macroH2A is enriched at a critical set of Utx target genes whose expression is critical for the early stages of induced pluripotency, and that macroH2A plays a role as a barrier to tumorigenesis.
 
References
Kapoor, A., Goldberg, M. S., Cumberland, L. K., Ratnakumar, K., Segura, M. F., Emanuel, P. O., Menendez, S., Vardabasso, C., LeRoy, G., Vidal, C. I., Polsky, D., Osman, I., Garcia, B. A., Hernando, E., & Bernstein, E. (2010). The histone variant macroH2A suppresses melanoma progression through regulation of CDK8. Nature, 468(7327), 1105–1109. https://doi.org/10.1038/nature09590
Vardabasso, C., Gaspar-Maia, A., Hasson, D., Pünzeler, S., Valle-Garcia, D., Straub, T., Keilhauer, E. C., Strub, T., Dong, J., Panda, T., Chung, C.-Y., Yao, J. L., Singh, R., Segura, M. F., Fontanals-Cirera, B., Verma, A., Mann, M., Hernando, E., Hake, S. B., & Bernstein, E. (2015). Histone Variant H2A.Z.2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma. Molecular Cell, 59(1), 75–88. https://doi.org/10.1016/j.molcel.2015.05.009
Sun, Zhen, Dan Filipescu, Joshua Andrade, Alexandre Gaspar-Maia, Beatrix Ueberheide, and Emily Bernstein. 2018. “Transcription-Associated Histone Pruning Demarcates MacroH2A Chromatin Domains.” Nature Structural & Molecular Biology 25(10):958–70. doi: 10.1038/s41594-018-0134-5.
 
Related Episodes
Influence of Histone Variants on Chromatin Structure and Metabolism (Marcus Buschbeck)
Regulation of Chromatin Organization by Histone Chaperones (Geneviève Almouzni)
Variants of Core Histones: Modulators of Chromatin Structure and Function (Sandra Hake)
 
Contact
Active Motif on Twitter
Epigenetics Podcast on Twitter
Active Motif on LinkedIn
Active Motif on Facebook
Email: podcast@activemotif.com

Spatio-Temporal Alterations in Chromosome Dynamics (Jane Skok)

In this episode of the Epigenetics Podcast, we caught up with Jane Skok from New York University School of Medicine to talk about her work on spatio-temporal alterations in chromosome dynamics.
Studies demonstrating that nuclear organization and long-range chromatin interactions play essential roles in gene regulation have been the focus of the Skok Lab, where the team has played a leading role. Their initial studies focused on lymphocyte development and the control of V(D)J recombination, a key part of generating the diverse repertoire of B-cell antibodies and T-cell receptors. The Skok Lab was among the first to demonstrate the possibility of chromatin forming dynamic loops which lead to the formation of reversible intra-locus loops in the immunoglobulin and T-cell receptor loci and to a profound impact on the ability of B and T cells to generate receptor diversity.
 
References
Roldán, E., Fuxa, M., Chong, W., Martinez, D., Novatchkova, M., Busslinger, M., & Skok, J. A. (2005). Locus “decontraction” and centromeric recruitment contribute to allelic exclusion of the immunoglobulin heavy-chain gene. Nature Immunology, 6(1), 31–41. https://doi.org/10.1038/ni1150
Skok, J. A. (2014). Taking a break from the lab: Can it really be done? Trends in Cell Biology, 24(12), 725–726. https://doi.org/10.1016/j.tcb.2014.09.002
Proudhon, C., Snetkova, V., Raviram, R., Lobry, C., Badri, S., Jiang, T., Hao, B., Trimarchi, T., Kluger, Y., Aifantis, I., Bonneau, R., & Skok, J. A. (2016). Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation. Cell Reports, 15(10), 2159–2169. https://doi.org/10.1016/j.celrep.2016.04.087
Lhoumaud, P., Sethia, G., Izzo, F., Sakellaropoulos, T., Snetkova, V., Vidal, S., Badri, S., Cornwell, M., Di Giammartino, D. C., Kim, K.-T., Apostolou, E., Stadtfeld, M., Landau, D. A., & Skok, J. (2019). EpiMethylTag: Simultaneous detection of ATAC-seq or ChIP-seq signals with DNA methylation. Genome Biology, 20(1), 248. https://doi.org/10.1186/s13059-019-1853-6
Nishana, M., Ha, C., Rodriguez-Hernaez, J., Ranjbaran, A., Chio, E., Nora, E. P., Badri, S. B., Kloetgen, A., Bruneau, B. G., Tsirigos, A., & Skok, J. A. (2020). Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation. Genome Biology, 21(1), 108. https://doi.org/10.1186/s13059-020-02024-0
 
Related Episodes
Identification of Functional Elements in the Genome (Bing Ren)
Spatial Organization of the Human Genome (Wendy Bickmore)
Chromatin Organization (Susan Gasser)
 
Contact
Active Motif on Twitter
Epigenetics Podcast on Twitter
Active Motif on LinkedIn
Active Motif on Facebook
Email: podcast@activemotif.com

Chromatin Organization During Development and Disease (Marieke Oudelaar)

In this episode of the Epigenetics Podcast, we caught up with Marieke Oudelaar from the Max Planck Institute for Biophysical Chemistry to talk about her work on chromatin organization during development and disease.
Marieke Oudelaar and her team focus on on developing high-resolution Chromosome Conformation Capture (3C) based techniques, like low-input Capture-C, Tri-C, and Tiled-C. Those techniques are then used in combination with other genomic techniques, genetic perturbations, and computational approaches to investigate the 3D structure of chromatin in development and disease. The team focused on the interplay between genome organisation and regulation during mammalian differentiation, and how perturbations in these processes contribute to human disease, including cancer.
 
References
Oudelaar, A. M., Davies, J. O. J., Downes, D. J., Higgs, D. R., & Hughes, J. R. (2017). Robust detection of chromosomal interactions from small numbers of cells using low-input Capture-C. Nucleic Acids Research, 45(22), e184–e184. https://doi.org/10.1093/nar/gkx1194
Oudelaar, A. M., Davies, J. O. J., Hanssen, L. L. P., Telenius, J. M., Schwessinger, R., Liu, Y., Brown, J. M., Downes, D. J., Chiariello, A. M., Bianco, S., Nicodemi, M., Buckle, V. J., Dekker, J., Higgs, D. R., & Hughes, J. R. (2018). Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains. Nature Genetics, 50(12), 1744–1751. https://doi.org/10.1038/s41588-018-0253-2
Oudelaar, A. M., Beagrie, R. A., Gosden, M., de Ornellas, S., Georgiades, E., Kerry, J., Hidalgo, D., Carrelha, J., Shivalingam, A., El-Sagheer, A. H., Telenius, J. M., Brown, T., Buckle, V. J., Socolovsky, M., Higgs, D. R., & Hughes, J. R. (2020). Dynamics of the 4D genome during in vivo lineage specification and differentiation. Nature Communications, 11(1), 2722. https://doi.org/10.1038/s41467-020-16598-7
Aljahani, A., Hua, P., Karpinska, M. A., Quililan, K., Davies, J. O. J., & Oudelaar, A. M. (2021). Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF [Preprint]. Genomics. https://doi.org/10.1101/2021.08.10.455796
 
Related Episodes
Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)
Unraveling Mechanisms of Chromosome Formation (Job Dekker)
Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)
 
Contact
Active Motif on Twitter
Epigenetics Podcast on Twitter
Active Motif on LinkedIn
Active Motif on Facebook
Email: podcast@activemotif.com