Episodes
Episodes
Thursday Jan 26, 2023
Molecular Mechanisms of Chromatin Modifying Enzymes (Karim-Jean Armache)
Thursday Jan 26, 2023
Thursday Jan 26, 2023
In this episode of the Epigenetics Podcast, we caught up with Karim-Jean Armache from New York University - Grossman School of Medicine to talk about his work on the structural analysis of Polycomb Complex Proteins and molecular mechanisms of chromatin modifying enzymes.
Karim-Jean Armache started his research career with the structural characterization of the 12-subunit RNA Polymerase II. After starting his own lab he used this knowledge in x-ray crystallography and electron microscopy to study how gene silencing complexes like the PRC complex act on chromatin and influence transcription. Further work in the Armache Lab focused on Dot, a histone H3K79 methyltransferase, and how it acts on chromatin, as well as how it is regulated by Histone-Histone crosstalk.
References
Armache, K. J., Garlick, J. D., Canzio, D., Narlikar, G. J., & Kingston, R. E. (2011). Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 Å resolution. Science (New York, N.Y.), 334(6058), 977–982. https://doi.org/10.1126/science.1210915
Lee, C. H., Holder, M., Grau, D., Saldaña-Meyer, R., Yu, J. R., Ganai, R. A., Zhang, J., Wang, M., LeRoy, G., Dobenecker, M. W., Reinberg, D., & Armache, K. J. (2018). Distinct Stimulatory Mechanisms Regulate the Catalytic Activity of Polycomb Repressive Complex 2. Molecular cell, 70(3), 435–448.e5. https://doi.org/10.1016/j.molcel.2018.03.019
De Ioannes, P., Leon, V. A., Kuang, Z., Wang, M., Boeke, J. D., Hochwagen, A., & Armache, K. J. (2019). Structure and function of the Orc1 BAH-nucleosome complex. Nature communications, 10(1), 2894. https://doi.org/10.1038/s41467-019-10609-y
Valencia-Sánchez, M. I., De Ioannes, P., Wang, M., Truong, D. M., Lee, R., Armache, J. P., Boeke, J. D., & Armache, K. J. (2021). Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation. Science (New York, N.Y.), 371(6527), eabc6663. https://doi.org/10.1126/science.abc6663
Related Episodes
Transcription and Polycomb in Inheritance and Disease (Danny Reinberg)
From Nucleosome Structure to Function (Karolin Luger)
Oncohistones as Drivers of Pediatric Brain Tumors (Nada Jabado)
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Thursday Jan 12, 2023
The Role of PHF13 in Chromatin and Transcription (Sarah Kinkley)
Thursday Jan 12, 2023
Thursday Jan 12, 2023
In this episode of the Epigenetics Podcast, we caught up with Sarah Kinkley from the Max Planck Institute of Molecular Genetics to talk about her work on PHF13 and its role in chromatin and transcription.
The Kinkley laboratory focuses mainly on unraveling the mechanism of action of the transcription factor PHF13 (PHC Finger Protein 13). PHF13 is a reader of the epigenetic mark H3K4 trimethylation which influences higher chromatin order, transcriptional regulation, and differentiation. The lab has shown that PHF13 plays a crucial role in phase separation and mitotic chromatin compaction.
References
Kinkley, S., Staege, H., Mohrmann, G., Rohaly, G., Schaub, T., Kremmer, E., Winterpacht, A., & Will, H. (2009). SPOC1: a novel PHD-containing protein modulating chromatin structure and mitotic chromosome condensation. Journal of cell science, 122(Pt 16), 2946–2956. https://doi.org/10.1242/jcs.047365
Chung, H. R., Xu, C., Fuchs, A., Mund, A., Lange, M., Staege, H., Schubert, T., Bian, C., Dunkel, I., Eberharter, A., Regnard, C., Klinker, H., Meierhofer, D., Cozzuto, L., Winterpacht, A., Di Croce, L., Min, J., Will, H., & Kinkley, S. (2016). PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3. eLife, 5, e10607. https://doi.org/10.7554/eLife.10607
Connecting the Dots: PHF13 and cohesin promote polymer-polymer phase separation of chromatin into chromosomes. Francesca Rossi, Rene Buschow, Laura V. Glaser, Tobias Schubert, Hannah Staege, Astrid Grimme, Hans Will, Thorsten Milke, Martin Vingron, Andrea M. Chiariello, Sarah Kinkley. bioRxiv 2022.03.04.482956; doi: https://doi.org/10.1101/2022.03.04.482956
Related Episodes
The Role of Blimp-1 in Immune-Cell Differentiation (Erna Magnúsdóttir)
H3K4me3, SET Proteins, Isw1, and their Role in Transcription (Jane Mellor)
The Role of SMCHD1 in Development and Disease (Marnie Blewitt)
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Thursday Dec 15, 2022
Genome Organization Mediated by RNA Polymerase II (Argyrys Papantonis)
Thursday Dec 15, 2022
Thursday Dec 15, 2022
In this episode of the Epigenetics Podcast, we caught up with Akis Papantonis from the University Medical Center Göttingen to talk about his work on genome organisation mediated by RNA Polymerase II.
The research of the Papantonis Laboratory focuses on investigating how environmental signalling stimuli are integrated by chromatin to control homeostatic to deregulated functional transitions. In more detail, the team is interested in how dynamic higher-order regulatory networks are influenced by the underlying linear DNA fiber. The ultimate goal of the laboratory is to understand general rules governing transcriptional and chromatin homeostasis and finally, how those rules might affect development, ageing or malignancies.
References
Larkin, J. D., Cook, P. R., & Papantonis, A. (2012). Dynamic reconfiguration of long human genes during one transcription cycle. Molecular and cellular biology, 32(14), 2738–2747. https://doi.org/10.1128/MCB.00179-12
Diermeier, S., Kolovos, P., Heizinger, L., Schwartz, U., Georgomanolis, T., Zirkel, A., Wedemann, G., Grosveld, F., Knoch, T. A., Merkl, R., Cook, P. R., Längst, G., & Papantonis, A. (2014). TNFα signalling primes chromatin for NF-κB binding and induces rapid and widespread nucleosome repositioning. Genome biology, 15(12), 536. https://doi.org/10.1186/s13059-014-0536-6
Sofiadis, K., Josipovic, N., Nikolic, M., Kargapolova, Y., Übelmesser, N., Varamogianni-Mamatsi, V., Zirkel, A., Papadionysiou, I., Loughran, G., Keane, J., Michel, A., Gusmao, E. G., Becker, C., Altmüller, J., Georgomanolis, T., Mizi, A., & Papantonis, A. (2021). HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence. Molecular systems biology, 17(6), e9760. https://doi.org/10.15252/msb.20209760
Enhancer-promoter contact formation requires RNAPII and antagonizes loop extrusion. Shu Zhang, Nadine Übelmesser, Mariano Barbieri, Argyris Papantonis. bioRxiv 2022.07.04.498738; doi: https://doi.org/10.1101/2022.07.04.498738
Related Episodes
Chromatin Organization During Development and Disease (Marieke Oudelaar)
Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)
Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)
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Thursday Dec 01, 2022
Thursday Dec 01, 2022
In this episode of the Epigenetics Podcast, we caught up with Melissa Harrison from the University of Wisconsin-Madison to talk about her work on the “Pioneer” Transcription Factors - Zelda and Grainyhead - and their role at the maternal-to-zygotic transition.
The Harrison lab studies how differentiation and development are driven by coordinated changes in gene expression. To do this, the targets of choice are the transcription factors Zelda and Grainyhead that bind to the genome at specific and crucial points in development and differentiation. These specialised transcription factors have the ability to bind to DNA in the context of nucleosomes which defines regulatory elements and leads to subsequent binding of additional classical transcription factors. These properties allow pioneer factors to act at the top of gene regulatory networks and control developmental transitions.
References
Harrison, M. M., Botchan, M. R., & Cline, T. W. (2010). Grainyhead and Zelda compete for binding to the promoters of the earliest-expressed Drosophila genes. Developmental biology, 345(2), 248–255. https://doi.org/10.1016/j.ydbio.2010.06.026
Harrison, M. M., Li, X. Y., Kaplan, T., Botchan, M. R., & Eisen, M. B. (2011). Zelda binding in the early Drosophila melanogaster embryo marks regions subsequently activated at the maternal-to-zygotic transition. PLoS genetics, 7(10), e1002266. https://doi.org/10.1371/journal.pgen.1002266
McDaniel, S. L., Gibson, T. J., Schulz, K. N., Fernandez Garcia, M., Nevil, M., Jain, S. U., Lewis, P. W., Zaret, K. S., & Harrison, M. M. (2019). Continued Activity of the Pioneer Factor Zelda Is Required to Drive Zygotic Genome Activation. Molecular cell, 74(1), 185–195.e4. https://doi.org/10.1016/j.molcel.2019.01.014
McDaniel, S. L., & Harrison, M. M. (2019). Optogenetic Inactivation of Transcription Factors in the Early Embryo of Drosophila. Bio-protocol, 9(13), e3296. https://doi.org/10.21769/BioProtoc.3296
Larson, E.D., Komori, H., Gibson, T.J. et al. Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila. Nat Commun 12, 7153 (2021). https://doi.org/10.1038/s41467-021-27506-y
Related Episodes
Pioneer Transcription Factors and Their Influence on Chromatin Structure (Ken Zaret)
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Thursday Nov 17, 2022
Epigenetics in Human Malaria Parasites (Elena Gómez-Diaz)
Thursday Nov 17, 2022
Thursday Nov 17, 2022
In this episode of the Epigenetics Podcast, we caught up with Elena Gomez-Diaz from the Institute of Parasitology and Biomedicine López-Neyra at the Spanish National Research Council. She share with us her work on the Epigenetics in Human Malaria Parasites.
Elena Gómez-Díaz and her team are focusing on understanding how epigenetic processes are implicated in host-parasite interactions by regulating gene expression in the model of malaria. The team has started to investigate and uncover layers of chromatin regulation that control developmental transitions in Plasmodium falciparum, especially in the parts of the life cycle that take place in the mosquito. Furthermore, the lab has investigated epigenetic changes that are present in malaria-infected Anopheles mosquitos, this led to the identification of cis-regulatory elements and enhancer-promoter networks in response to infection.
References
Gómez-Díaz E, Rivero A, Chandre F, Corces VG. Insights into the epigenomic landscape of the human malaria vector Anopheles gambiae. Front Genet. 2014 Aug 15;5:277. doi: 10.3389/fgene.2014.00277. PMID: 25177345; PMCID: PMC4133732.
Gómez-Díaz, E., Yerbanga, R., Lefèvre, T. et al. Epigenetic regulation of Plasmodium falciparum clonally variant gene expression during development in Anopheles gambiae. Sci Rep 7, 40655 (2017). https://doi.org/10.1038/srep40655
José Luis Ruiz, Juan J Tena, Cristina Bancells, Alfred Cortés, José Luis Gómez-Skarmeta, Elena Gómez-Díaz, Characterization of the accessible genome in the human malaria parasite. Plasmodium falciparum, Nucleic Acids Research, Volume 46, Issue 18, 12 October 2018, Pages 9414–9431, https://doi.org/10.1093/nar/gky643
Women in Malaria 2021: A Conference Premier. (2021). Trends in Parasitology, 37(7), 573–580. https://doi.org/10.1016/j.pt.2021.04.001
Twitter Account: https://twitter.com/womeninmalaria
Related Episodes
Multiple challenges of CUT&Tag (Cassidee McDonough, Kyle Tanguay)
ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells (Jason Buenrostro)
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Thursday Nov 03, 2022
Bioinformatic Analysis in Epigenetics Research (Nick Pervolarakis)
Thursday Nov 03, 2022
Thursday Nov 03, 2022
In this episode of the Epigenetics Podcast, we caught up with Nick Pervolarakis from Active Motif to talk about bioinformatic analysis in epigenetics research.
While many “bench scientists” are familiar with the workflows of ChIP-Seq, ATAC-Seq and CUT&Tag, and even the preparation and analysis of the libraries, the steps between sequencing and fully analyzed data is sometimes thought of as a mystery known only to bioinformatic experts. Most of us have some understanding that the raw data is usually in a file format called a FASTQ. But how do we get from FASTQ files to peaks on a genome browser? This Podcast Episode will provide a peek behind the curtain of the informatic analysis we perform at Active Motif, as part of our end-to-end epigenetic services.
References
Life in the FASTQ Lane
Bioinformatics Resource Center
Epigenetic Services
Related Episodes
Multiple challenges of ATAC-Seq, Points to Consider (Yuan Xue)
Multiple challenges of CUT&Tag (Cassidee McDonough, Kyle Tanguay)
Multiple Challenges in ChIP (Adam Blattler)
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Thursday Oct 20, 2022
Anchor-Based Bisulfite Sequencing (Ben Delatte)
Thursday Oct 20, 2022
Thursday Oct 20, 2022
In this episode of the Epigenetics Podcast, we caught up with Ben Delatte Research Scientist at Active Motif to talk about his work on Anchor Based Bisulfite Sequencing.
Whole Genome Bisulfite Sequencing (WGBS) is the current standard for DNA methylation profiling. However, this approach is costly as it requires sequencing coverage over the entire genome. Here we introduce Anchor-Based Bisulfite Sequencing (ABBS). ABBS captures accurate DNA methylation information in Escherichia coli and mammals, while requiring up to 10 times fewer sequencing reads than WGBS. ABBS interrogates the entire genome and is not restricted to the CpG islands assayed by methods like Reduced Representation Bisulfite Sequencing (RRBS). The ABBS protocol is simple and can be performed in a single day.
References
Chapin, N., Fernandez, J., Poole, J. et al. Anchor-based bisulfite sequencing determines genome-wide DNA methylation. Commun Biol 5, 596 (2022). https://doi.org/10.1038/s42003-022-03543-1
Related Episodes
The Role of DNA Methylation in Epilepsy (Katja Kobow)
DNA Methylation and Mammalian Development (Déborah Bourc'his)
Effects of DNA Methylation on Diabetes (Charlotte Ling)
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Thursday Oct 06, 2022
Enhancer Communities in Adipocyte Differentiation (Susanne Mandrup)
Thursday Oct 06, 2022
Thursday Oct 06, 2022
In this episode of the Epigenetics Podcast, we caught up with Susanne Mandrup from the University of Southern Denmark to talk about her work on the role of enhancer communities in adipocyte differentiation.
The Laboratory of Susanne Mandrup focuses on the effect of enhancers and enhancer communities on the differentiation of mesenchymal stem cell into adipocytes and osteoblasts. The team has shown that there is significant cross-talk between enhancers and that these form communities of highly interconnected enhancers. Inactive enhancers are then activated by association with these pre-existing enhancer networks to facilitate gene expression in adipocyte differentiation.
References
Siersbæk R, Rabiee A, Nielsen R, Sidoli S, Traynor S, Loft A, Poulsen LC, Rogowska-Wrzesinska A, Jensen ON, Mandrup S. Transcription factor cooperativity in early adipogenic hotspots and super-enhancers. Cell Rep. 2014 Jun 12;7(5):1443-1455. doi: 10.1016/j.celrep.2014.04.042. Epub 2014 May 22. PMID: 24857652.
Siersbæk R, Baek S, Rabiee A, Nielsen R, Traynor S, Clark N, Sandelin A, Jensen ON, Sung MH, Hager GL, Mandrup S. Molecular architecture of transcription factor hotspots in early adipogenesis. Cell Rep. 2014 Jun 12;7(5):1434-1442. doi: 10.1016/j.celrep.2014.04.043. Epub 2014 May 22. PMID: 24857666; PMCID: PMC6360525.
Siersbæk R, Madsen JGS, Javierre BM, Nielsen R, Bagge EK, Cairns J, Wingett SW, Traynor S, Spivakov M, Fraser P, Mandrup S. Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation. Mol Cell. 2017 May 4;66(3):420-435.e5. doi: 10.1016/j.molcel.2017.04.010. PMID: 28475875.
Rauch, A., Haakonsson, A.K., Madsen, J.G.S. et al. Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis. Nat Genet 51, 716–727 (2019). https://doi.org/10.1038/s41588-019-0359-1
Madsen, J.G.S., Madsen, M.S., Rauch, A. et al. Highly interconnected enhancer communities control lineage-determining genes in human mesenchymal stem cells. Nat Genet 52, 1227–1238 (2020). https://doi.org/10.1038/s41588-020-0709-z
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Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)
Effects of DNA Methylation on Diabetes (Charlotte Ling)
Epigenetic Regulation of Stem Cell Self-Renewal and Differentiation (Peggy Goodell)
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