Epigenetics Podcast

Epigenetics & Glioblastoma: New Approaches to Treat Brain Cancer (Lucy Stead)

In this Episode of the Epigenetics Podcast our guest Lucy Stead from the University of Leeds provides insight into her work on intratumor heterogeneity in Glioblastoma. In order to tackle this area she uses an holistic approach including Computational Genomics, In silico Modeling and Functional Genomics in order to test whether treatment-resistant subclones emerge in recurrent tumors, and characterize them in clinically relevant ways in multiple patients. And this is just a glimpse of what is discussed in this Episode.
 
References 
Lucy F. Stead, Helene Thygesen, … Pamela Rabbitts (2015) Using common variants to indicate cancer genes (International Journal of Cancer) DOI: 10.1002/ijc.28951 
Caroline Conway, Jennifer L. Graham, … Lucy F. Stead (2015) Elucidating drivers of oral epithelial dysplasia formation and malignant transformation to cancer using RNAseq (Oncotarget) DOI: 10.18632/oncotarget.5529 
Alastair Droop, Alexander Bruns, … Lucy F. Stead (2018) How to analyse the spatiotemporal tumour samples needed to investigate cancer evolution: A case study using paired primary and recurrent glioblastoma (International Journal of Cancer) DOI: 10.1002/ijc.31184 
Georgette Tanner, David R. Westhead, … Lucy F. Stead (2019) Simulation of heterogeneous tumour genomes with HeteroGenesis and in silico whole exome sequencing (Bioinformatics (Oxford, England)) DOI: 10.1093/bioinformatics/bty1063 
Nora Rippaus, Alexander F-Bruns, … Lucy F. Stead (2019) JARID2 facilitates transcriptional reprogramming in glioblastoma in response to standard treatment (bioRxiv) DOI: 10.1101/649400
 
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The Past, Present, and Future of Epigenetics (Joe Fernandez, founder of Active Motif)

Joe Fernandez, the founder of Active Motif, has played a significant role in the evolution of the biotechnology industry. He’s seen where the industry has been, and he has a good idea where it’s going. 
Prior to founding Active Motif in 1999, Joe was a co-founder of Invitrogen where he helped revolutionize molecular cloning with the TOPO TA kit. Joe’s passion for disrupting established workflows by making them easier and more efficient didn’t stop there. With Active Motif, he launched the first ever ChIP kit in 2003, and the company now offers the most complete portfolio of ChIP kits for different workflows and sample types, the highest quality ChIP-validated antibodies, and the most comprehensive and most cited end-to-end Epigenetic Services. 
In this interview, we sat down with Joe to learn how he got started in science, what he’s currently excited about, and what he thinks will be the next big thing in epigenetics research.  
 
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The Interchromatin Network Model (Ana Pombo)

In this Episode of the Epigenetics Podcast our guest Ana Pombo from the Max-Delbrück-Center in Berlin provides insight in her work on the interplay between gene regulation and genome architecture. To do so she and her team use different state of the art methods, including cryo-sectioning to unravel this regulatory network. In 2006, they proposed the Interchromatin Network Model of chromosome organization which postulates that chromosome folding is driven by contacts between different genomic regions and between chromatin and nuclear landmarks, such as the nuclear lamina. And later on they used polymer physics modeling to study those mechanisms, which lead to the development of the Strings & Binders Switch (SBS) model. And this is just a glimpse of the topics that are discussed in this Episode.
 
References
Miguel R. Branco, Ana Pombo (2006) Intermingling of Chromosome Territories in Interphase Suggests Role in Translocations and Transcription-Dependent Associations (PLOS Biology) DOI: 10.1371/journal.pbio.0040138 
Robert A. Beagrie, Ana Pombo (2016) Gene activation by metazoan enhancers: Diverse mechanisms stimulate distinct steps of transcription (BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology) DOI: 10.1002/bies.201600032 
Emily Brookes, Inês de Santiago, … Ana Pombo (2012) Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs (Cell Stem Cell) DOI: 10.1016/j.stem.2011.12.017 
Mario Nicodemi, Ana Pombo (2014) Models of chromosome structure (Current Opinion in Cell Biology) DOI: 10.1016/j.ceb.2014.04.004 - Robert A. Beagrie, Antonio Scialdone, … Ana Pombo (2017) Complex multi-enhancer contacts captured by genome architecture mapping (Nature) DOI: 10.1038/nature21411
 
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Dosage Compensation in Drosophila (Asifa Akhtar)

Dosage compensation is an essential process to regulate the gene expression of the X-chromosome in female and male flies. Thereby the mechanism of regulation in humans and in drosophila is different. In humans one X-chromosome is randomly shut down in females compared to men, whereas in drosophila equilibrium is achieved by overexpression of the single X-chromosome in males. In this Episode our guest Dr. Asifa Akhtar provides information on her work on dosage compensation in drosophila melanogaster and how the MSL-complex, the Histone-acetyltransferase MOF work together in this process. Furthermore, she also talks about potential functions of those Proteins in the human system.
 
References 
Jan Kadlec, Erinc Hallacli, … Asifa Akhtar (2011) Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1 (Nature Structural & Molecular Biology) DOI: 10.1038/nsmb.1960 
Thomas Conrad, Florence M.G. Cavalli, … Asifa Akhtar (2012) The MOF Chromobarrel Domain Controls Genome-wide H4K16 Acetylation and Spreading of the MSL Complex (Developmental Cell) DOI: 10.1016/j.devcel.2011.12.016 
Maria Samata, Asifa Akhtar (2018) Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs (Annual Review of Biochemistry) DOI: 10.1146/annurev-biochem-062917-011816 
Bilal N. Sheikh, Sukanya Guhathakurta, Asifa Akhtar (2019) The non-specific lethal (NSL) complex at the crossroads of transcriptional control and cellular homeostasis (EMBO reports) DOI: 10.15252/embr.201847630 
Kin Chung Lam, Ho-Ryun Chung, … Asifa Akhtar (2019) The NSL complex-mediated nucleosome landscape is required to maintain transcription fidelity and suppression of transcription noise (Genes & Development) DOI: 10.1101/gad.321489.118 
Claudia Isabelle Keller Valsecchi, M. Felicia Basilicata, … Asifa Akhtar (2018) Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells (Nature Communications) DOI: 10.1038/s41467-018-05642-2
 
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Spatial Organization of the Human Genome (Wendy Bickmore)

In recent years it has become more and more evident, that genome folding and chromatin packaging into the nucleus plays a pivotal role in the regulation of gene expression. In this Episode of our Podcast our host Dr. Stefan Dillinger spoke with Professor Wendy Bickmore about her work on the spatial organization of the human genome. Prof. Bickmore and her team mainly use visual methods like fluorescence in situ hybridisation (FISH) to study the organization of chromosomes in human and murine cells and how they contribute to transcriptional regulation and how this organization changes during ageing, development or disease.
References
Charlene Boumendil, Priya Hari, … Wendy A. Bickmore (2019) Nuclear pore density controls heterochromatin reorganization during senescence (Genes & Development) DOI: 10.1101/gad.321117.118 
Charlene Lemaître, Wendy A. Bickmore (2015) Chromatin at the nuclear periphery and the regulation of genome functions (Histochemistry and Cell Biology) DOI: 10.1007/s00418-015-1346-y 
James Fraser, Iain Williamson, … Josée Dostie (2015) An Overview of Genome Organization and How We Got There: from FISH to Hi-C (Microbiology and Molecular Biology Reviews) DOI: 10.1128/MMBR.00006-15 
Emmanuelle Deniaud, Wendy A Bickmore (2009) Transcription and the nuclear periphery: edge of darkness? (Current Opinion in Genetics & Development) DOI: 10.1016/j.gde.2009.01.005 
Nicola L. Mahy, Paul E. Perry, … Wendy A. Bickmore (2002) Spatial organization of active and inactive genes and noncoding DNA within chromosome territories (The Journal of Cell Biology) DOI: 10.1083/jcb.200111071
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Heterochromatin and Phase Separation (Gary Karpen)

Heterochromatin plays a pivotal role in organizing our genome in the nucleus and separating active from inactive genomic regions. In this Podcast Episode our Guest Gary Karpen from UC Berkeley sits down with our Host Stefan Dillinger to talk about the regulation of this chromatin structure and how DNA repair mechanisms function in this densely packed nuclear compartment. Furthermore, they also discuss how phase separation might be an important part in how heterochromatin domains are formed.
References
Jamy C. Peng, Gary H. Karpen (2009) Heterochromatic Genome Stability Requires Regulators of Histone H3 K9 Methylation (PLoS Genetics) DOI: 10.1371/journal.pgen.1000435
Peter V. Kharchenko, Artyom A. Alekseyenko, … Peter J. Park (2011) Comprehensive analysis of the chromatin landscape in Drosophila melanogaster (Nature) DOI: 10.1038/nature09725
Aniek Janssen, Serafin U. Colmenares, … Gary H. Karpen (2019) Timely double-strand break repair and pathway choice in pericentromeric heterochromatin depend on the histone demethylase dKDM4A (Genes & Development) DOI: 10.1101/gad.317537.118 
Amy R. Strom, Alexander V. Emelyanov, … Gary H. Karpen (2017) Phase separation drives heterochromatin domain formation (Nature) DOI: 10.1038/nature22989
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Diabetes and Epigenetics (Jean-Sébastien Annicotte)

Type 2 Diabetes (T2D) is a chronic metabolic disease, which is caused by the failure of beta-cells in the pancreas and insulin resistance in peripheral tissue and characterized by high glucose levels in the blood. World-wide 382 Million people suffer from Diabetes which makes up 8,3% of the population. Due to this high proportion it is of high interest to find a cure for this disease.
The restoration of β-cell mass and function has therefore become a field of intensive research seeking for the next generation of anti-diabetic drugs. Tremendous efforts have been made on deciphering epigenetic regulations that control metabolic tissue function. For several years, the team led by Dr. Jean-Sebastien Annicotte has dissected the molecular links between insulin producing cells, insulin target tissues and T2D/obesity development. Especially, the team research has been focused on the role of cell cycle regulators and their transcriptional co-regulators in the control of metabolic homeostasis, T2D and obesity.
 
References
Jean-Sébastien Annicotte, Elisabeth Fayard, … Johan Auwerx (2003) Pancreatic-Duodenal Homeobox 1 Regulates Expression of Liver Receptor Homolog 1 during Pancreas Development (Molecular and Cellular Biology) DOI: 10.1128/MCB.23.19.6713-6724.2003 
Jean-Sébastien Annicotte, Emilie Blanchet, … Lluis Fajas (2009) The CDK4-pRB-E2F1 pathway controls insulin secretion (Nature Cell Biology) DOI: 10.1038/ncb1915 
Emilie Blanchet, Jean-Sébastien Annicotte, … Lluis Fajas (2011) E2F transcription factor-1 regulates oxidative metabolism (Nature Cell Biology) DOI: 10.1038/ncb2309
Nabil Rabhi, Pierre-Damien Denechaud, … Jean-Sébastien Annicotte (2016) KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response (Cell Reports) DOI: 10.1016/j.celrep.2016.03.079
Albert Giralt, Pierre-Damien Denechaud, … Lluis Fajas (2018) E2F1 promotes hepatic gluconeogenesis and contributes to hyperglycemia during diabetes (Molecular Metabolism) DOI: 10.1016/j.molmet.2018.02.011
 
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Epigenetics and X-inactivation (Edith Heard)

In the seventh Episode of Active Motif's Epigenetics Podcast our host Dr. Stefan Dillinger sat down with Prof. Edith Heard, designated Director General of the European Molecular Biology Laboratory (EMBL), to talk about the challenges and goals of her new position as Director General of the EMBL. Furthermore, they also talk about her research on X-inactivation and dosage compensation.
 
References
Heard Lab - https://science.institut-curie.org/research/biology-cancer-genetics-and-epigenetics/developmental-biology-and-genetics/team-heard/
Elphège P. Nora, Bryan R. Lajoie, … Edith Heard (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre (Nature) DOI: 10.1038/nature11049 
Luca Giorgetti, Bryan R. Lajoie, … Job Dekker (2016) Structural organization of the inactive X chromosome in the mouse (Nature) DOI: 10.1038/nature18589 
Luca Giorgetti, Rafael Galupa, … Edith Heard (2014) Predictive Polymer Modeling Reveals Coupled Fluctuations in Chromosome Conformation and Transcription (Cell) DOI: 10.1016/j.cell.2014.03.025 
Maud Borensztein, Laurène Syx, … Edith Heard (2017) Xist-dependent imprinted X inactivation and the early developmental consequences of its failure (Nature Structural & Molecular Biology) DOI: 10.1038/nsmb.3365
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