Epigenetics Podcast

Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)

In this episode of the Epigenetics Podcast, we caught up with Erez Lieberman Aiden, Ph.D. from Baylor College of Medicine and Rice University in Houston to talk about his work on developing Hi-C and investigating the three-dimensional structure of the genome. He was the first author on a publication in the journal Science titled "Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome" which was the paper that first introduced the Hi-C method in 2009 and he has continued studying the structure of the chromosome ever since.
Erez Lieberman Aiden is currently an Assistant Professor in both the Department of Genetics at the Baylor College of Medicine, where he directs the newly-established Center for Genome Architecture, and in the Department of Computer Science and Computational and Applied Mathematics at Rice University across the street.
In this interview, we discuss the road that Erez Lieberman Aiden went down to optimize the Hi-C protocol, the hurdles he had to overcome, and how Hi-C made it possible to probe the three-dimensional structure of the genome.
References 
Erez Lieberman-Aiden, Nynke L. van Berkum, … Job Dekker (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome (Science (New York, N.Y.)) DOI: 10.1126/science.1181369 
Suhas S. P. Rao, Miriam H. Huntley, … Erez Lieberman Aiden (2014) A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping (Cell) DOI: 10.1016/j.cell.2014.11.021 
Adrian L. Sanborn, Suhas S. P. Rao, … Erez Lieberman Aiden (2015) Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes (Proceedings of the National Academy of Sciences) DOI: 10.1073/pnas.1518552112 
Suhas S.P. Rao, Su-Chen Huang, … Erez Lieberman Aiden (2017) Cohesin Loss Eliminates All Loop Domains (Cell) DOI: 10.1016/j.cell.2017.09.026
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Chromatin Structure and Dynamics at Ribosomal RNA Genes (Tom Moss)

In this episode of the Epigenetics Podcast, we caught up with Professor Tom Moss from Université Laval in Québec City, Canada to talk about his work on the chromatin structure and dynamics at ribosomal RNA genes.
Dr. Tom Moss has been a member of the Department of Molecular Biology, Medical Biochemistry, and Pathology at the Laval University School of Medicine since he was recruited from the University of Portsmouth in the United Kingdom in 1986.
Since then he focused on the ribosomal transcription factor Upstream Binding Factor (UBF) and how it regulates the chromatin structure at ribosomal RNA genes (rDNA). UBF binds to the rDNA as a dimer where it leads to six in-phase bends and induces the formation of the ribosomal enhanceosome. This enhanceosome is required for the initial step in formation of an RNA polymerase I initiation complex, and therefore plays an important role in regulating the expression of ribosomal RNA genes.
In this Interview, we discuss the function of UBF on the rDNA, how UBF impacts the chromatin landscape at rRNA genes, the role of DNA methylation in this process, and how UBF influences the structure of the nucleolus.
References
D. Bachvarov, T. Moss (1991) The RNA polymerase I transcription factor xUBF contains 5 tandemly repeated HMG homology boxes (Nucleic Acids Research) DOI: 10.1093/nar/19.9.2331
V. Y. Stefanovsky, D. P. Bazett-Jones, … T. Moss (1996) The DNA supercoiling architecture induced by the transcription factor xUBF requires three of its five HMG-boxes (Nucleic Acids Research) DOI: 10.1093/nar/24.16.3208
V. Y. Stefanovsky, G. Pelletier, … T. Moss (2001) DNA looping in the RNA polymerase I enhancesome is the result of non-cooperative in-phase bending by two UBF molecules (Nucleic Acids Research) DOI: 10.1093/nar/29.15.3241
Elaine Sanij, Jeannine Diesch, … Ross D. Hannan (2015) A novel role for the Pol I transcription factor UBTF in maintaining genome stability through the regulation of highly transcribed Pol II genes (Genome Research) DOI: 10.1101/gr.176115.114
Tom Moss, Jean-Clement Mars, … Marianne Sabourin-Felix (2019) The chromatin landscape of the ribosomal RNA genes in mouse and human (Chromosome Research) DOI: 10.1007/s10577-018-09603-9
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Epigenetic Origins Of Heterogeneity And Disease (Andrew Pospisilik)

In this episode of the Epigenetics Podcast, we caught up with Dr. Andrew Pospisilik from the Van Andel Institute in Grand Rapids, Michigan to talk about his work on the epigenetic origins of heterogeneity and disease.
Dr. Andrew Pospisilik worked at the Max-Planck Institute of Immunobiology and Epigenetics in Freiburg for 8 years and in 2018 he joined the Van Andel Institute as the director of its Center for Epigenetics. At the Van Andel Institute his research focuses on diabetes, neurodegenerative diseases, cancer, and obesity. The goal of the Pospisilik laboratory is to better understand epigenetic mechanisms of these diseases and the roles of epigenetics in disease susceptibility and heterogeneity.
 
These areas of medicine are among the most important public health challenges, with the latest estimates suggesting that they impact more than 1 billion people worldwide. Although these diverse conditions are all very different, they are now thought to be caused, at least partially, from alterations in the epigenetic mechanisms that regulate gene expression and metabolism. This interview covers recent work from the Pospisilik lab on the epigenetics of these complex diseases. 
 
References
https://pospisiliklab.vai.org/
J. Andrew Pospisilik, Daniel Schramek, … Josef M. Penninger (2010) Drosophila Genome-wide Obesity Screen Reveals Hedgehog as a Determinant of Brown versus White Adipose Cell Fate (Cell) DOI: 10.1016/j.cell.2009.12.027
Anita Öst, Adelheid Lempradl, … J. Andrew Pospisilik (2014) Paternal diet defines offspring chromatin state and intergenerational obesity (Cell) DOI: 10.1016/j.cell.2014.11.005
Kevin Dalgaard, Kathrin Landgraf, … J. Andrew Pospisilik (2016) Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity (Cell) DOI: 10.1016/j.cell.2015.12.025
Tess Tsai-Hsiu Lu, Steffen Heyne, … J. Andrew Pospisilik (2018) The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes (Cell Metabolism) DOI: 10.1016/j.cmet.2018.04.013
 
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PIXUL: On the Leading Edge of Chromatin Shearing (Karol Bomsztyk and Tom Matula)

In this episode of the Epigenetics Podcast, we caught up with Karol Bomsztyk M.D. and Tom Matula, Ph.D. from the University of Washington and Matchstick Technologies, to talk about their work on DNA and chromatin sonication.
During his career, Karol's research has focused on improving ChIP protocols to make them faster, easier and higher throughput. First, to make ChIP assays faster, Karol and his lab developed "Fast-ChIP". More recently, he adjusted this protocol to improve throughput and "Matrix-ChIP" was born. Tom is an expert in the field of ultrasound and cavitation and the Director of the Center for Industrial and Medical Ultrasound at the University of Washington.
To further improve and speed up the 96-well "Matrix-ChIP" protocol, Karol and Tom teamed up to found Matchstick Technologies and develop a sonication device that would be able to processes each and every well of a 96-well microplate consistently and quickly. The result of this cooperation is the PIXUL Multi-Sample Sonicator that is now available for order from Active Motif.
PIXUL is an ultrasound-based sample preparation platform that was designed completely from the ground up to provide researchers with an easy-to-use tool that is simple to set up, simple to use, and generates consistent results day in and day out. No other sample preparation platform out there can match the power and convenience of PIXUL.
PIXUL was conceived by an epigenetics researcher, and designed and built by ultrasound engineers to take the guesswork out of sample preparation. With PIXUL, sample preparation is no longer an art form, but instead a simple and predictable part of experiments that work every single time.
This interview goes into the mechanism behind sonication-based shearing of DNA and chromatin and highlights how PIXUL is different from existing sonication instruments.
 
References
http://activemotif.com/PIXUL
Karol Bomsztyk
Tom Matula
Innovation Imperative: New Device Speeds Disease Biomarker Search
  
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Influence of Histone Variants on Chromatin Structure and Metabolism (Markus Buschbeck)

In this episode of the Epigenetics Podcast, we sat down with Marcus Buschbeck, Group Leader at the Josep Carreras Leukaemia Research Institute in Barcelona, to talk about his work on the histone variant macroH2A, its role in metabolism and how it contributes to the regulation of chromatin structure.
 
Histone variants equip chromatin with unique properties and show a specific genomic distribution. The histone variant macroH2A is unique in having a tripartite structure consisting of a N-terminal histone-fold, an intrinsically unstructured linker domain and a C-terminal macro domain. Recent discoveries show that macroH2A proteins have a major role in the nuclear organization which has the potential to explain how these proteins can act as tumor suppressors, promoters of differentiation and barriers to somatic cell reprogramming.
 
We discuss these topics, the mission of the Josep Carreras Leukaemia Research Institute, and much more in this episode.
  
References
http://www.carrerasresearch.org/Buschbeck_Marcus
Marcus Buschbeck, Iris Uribesalgo, … Luciano Di Croce (2009) The histone variant macroH2A is an epigenetic regulator of key developmental genes (Nature Structural & Molecular Biology) DOI: 10.1038/nsmb.1665 
Julien Douet, David Corujo, … Marcus Buschbeck (2017) MacroH2A histone variants maintain nuclear organization and heterochromatin architecture (Journal of Cell Science) DOI: 10.1242/jcs.199216 
Melanija Posavec Marjanović, Sarah Hurtado-Bagès, … Marcus Buschbeck (2017) MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption (Nature Structural & Molecular Biology) DOI: 10.1038/nsmb.3481
Oriana Lo Re, Julien Douet, … Manlio Vinciguerra (2018) Histone variant macroH2A1 rewires carbohydrate and lipid metabolism of hepatocellular carcinoma cells towards cancer stem cells (Epigenetics) DOI: 10.1080/15592294.2018.1514239
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Epigenetic Mechanisms of Aging and Longevity (Shelley Berger)

In this Episode we sat down with Shelley Berger, Keynote Speaker at the "EMBO | EMBL Symposium: Metabolism Meets Epigenetics" to talk about her work on Epigenetic Mechanisms of Aging and Longevity. On how cytoplasmic chromatin fragments are involved in these processes, how alcohol has an effect on Histone PTMs in the brain and last but not least how Ants became her favorite Model Organism.
References
Hazel A. Cruickshanks, Tony McBryan, … Peter D. Adams (2013) Senescent cells harbour features of the cancer epigenome (Nature Cell Biology) DOI: 10.1038/ncb2879
Zhixun Dou, Kanad Ghosh, … Shelley L. Berger (2017) Cytoplasmic chromatin triggers inflammation in senescence and cancer (Nature) DOI: 10.1038/nature24050 
Hua Yan, Comzit Opachaloemphan, … Claude Desplan (2017) An Engineered orco Mutation Produces Aberrant Social Behavior and Defective Neural Development in Ants (Cell) DOI: 10.1016/j.cell.2017.06.051 
P. Mews, G. Egervari, … S. L. Berger (2019) Alcohol metabolism contributes to brain histone acetylation (Nature) DOI: 10.1038/s41586-019-1700-7 
Karl M. Glastad, Riley J. Graham, … Shelley L. Berger (2019) Epigenetic Regulator CoREST Controls Social Behavior in Ants (Molecular Cell) DOI: 10.1016/j.molcel.2019.10.012
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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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