Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)

Published: June 4, 2020, 7:26 a.m.

b'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.\\nLeonid 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.\\nFurthermore, 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.\\nIn 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.\\xa0\\n\\xa0\\nReferences \\nGrigory Kolesov, Zeba Wunderlich, \\u2026 Leonid A. Mirny (2007) How gene order is influenced by the biophysics of transcription regulation (Proceedings of the National Academy of Sciences) DOI: 10.1073/pnas.0700672104\\xa0\\nErez Lieberman-Aiden, Nynke L. van Berkum, \\u2026 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\\xa0\\nGeoffrey Fudenberg, Maxim Imakaev, \\u2026 Leonid A. Mirny (2016) Formation of Chromosomal Domains by Loop Extrusion (Cell Reports) DOI: 10.1016/j.celrep.2016.04.085\\xa0\\nJohannes Nuebler, Geoffrey Fudenberg, \\u2026 Leonid A. Mirny (2018) Chromatin organization by an interplay of loop extrusion and compartmental segregation (Proceedings of the National Academy of Sciences) DOI: 10.1073/pnas.1717730115\\xa0\\nMartin Falk, Yana Feodorova, \\u2026 Leonid A. Mirny (2019) Heterochromatin drives compartmentalization of inverted and conventional nuclei (Nature) DOI: 10.1038/s41586-019-1275-3\\n\\xa0\\nContact\\xa0\\nActive Motif on Twitter\\nEpigenetics Podcast on Twitter\\nActive Motif on Linked-In\\nActive Motif on Facebook\\neMail: podcast@activemotif.com'