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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The Role of Histone Dopaminylation and Serotinylation in Neuronal Plasticity (Ian Maze)
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Multimodal Characterization of Cellular Identity | CITE-Seq and Beyond (Peter Smibert, VP of 10X Genomics)
The Effect of Mechanotransduction on Chromatin Structure and Transcription in Stem Cells (Sara Wickström)
Single-Cell Technologies using Microfluidics (Ben Hindson, CSO of 10x Genomics)
Epigenome-based Precision Medicine (Eleni Tomazou)
Epigenetics and Epitranscriptomics in Cancer (Manel Esteller)
Enhancer-Promoter Interactions During Development (Yad Ghavi-Helm)
The Effect of Vitamin D on the Epigenome (Folami Ideraabdullah)
H3K4me3, Set-Proteins, Isw1 and their Role in Transcription (Jane Mellor)
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