In this episode of the Epigenetics Podcast, we caught up with Leonid Mirny, Ph.D., from MIT to talk about his work on biophysical modeling of the 3-D structure of chromatin.
Leonid Mirny was part of the initial Hi-C paper titled "Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome" that was published in 2009 in the journal Science. Since then, technology has evolved and Dr. Mirny's group has developed a method called Micro-C that improves the Hi-C protocol by using MNase digestion to increase the resolution to nucleosomal level. This led to the visualization of interactions that were already predicted by his previous biophysical models.
Furthermore, Leonid Mirny worked on finding the mechanism by which chromatin loops are formed. He and his team proposed that loop extrusion underlies TAD formation. In this process, factors like cohesin and CTCF form progressively larger loops but stall at TAD boundaries due to interactions of CTCF with TAD boundaries. He used polymer simulations to show that this model produces TADs and finer-scale features of Hi-C data. Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops.
In this interview, we chatted with Dr. Mirny about the details of Hi-C, the development of Micro-C and how it compares to Hi-C, and how biophysical modeling helps to unravel the mechanisms behind loop extrusion.
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Analysis of 3D Chromatin Structure Using Super-Resolution Imaging (Alistair Boettiger)
Gene Dosage Alterations in Evolution and Ageing (Claudia Keller Valsecchi)
Structural Analysis of Nucleosomes During Transcription (Lucas Farnung)
DNA Methylation Alterations in Neurodegenerative Diseases (Paula Desplats)
scDamID, EpiDamID and Lamina Associated Domains (Jop Kind)
Circulating Epigenetic Biomarkers in Cancer (Charlotte Proudhon)
Epigenetic Landscapes During Cancer (Luciano Di Croce)
Formation of CenH3-deficient Kinetochores (Ines Drinnenberg)
Effects of Environmental Cues on the Epigenome and Longevity (Paul Shiels)
The Epigenetics of Human Sperm Cells (Sarah Kimmins)
Transgenerational Inheritance and Evolution of Epimutations (Peter Sarkies)
Transcription Elongation Control by the Paf1 Complex (Karen Arndt)
Molecular Mechanisms of Chromatin Modifying Enzymes (Karim-Jean Armache)
The Role of PHF13 in Chromatin and Transcription (Sarah Kinkley)
Genome Organization Mediated by RNA Polymerase II (Argyrys Papantonis)
The Role of Pioneer Factors Zelda and Grainyhead at the Maternal-to-Zygotic Transition (Melissa Harrison)
Epigenetics in Human Malaria Parasites (Elena Gómez-Diaz)
Bioinformatic Analysis in Epigenetics Research (Nick Pervolarakis)
Anchor-Based Bisulfite Sequencing (Ben Delatte)
Enhancer Communities in Adipocyte Differentiation (Susanne Mandrup)
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