Leonid A. Mirny, PhD
Professor of Medical Engineering and Science, and Physics
Massachusetts Institute of Technology
Chromosome folding by loop extrusion
Earlier we suggested that loop extrusion by SMC complexes could be a universal mechanism responsible for formation of domains in interphase [1], chromosome compaction and segregation in mitosis [2]. I will present our recent results [3-7], which support this mechanism by showing that cohesin plays a central role in the loop extrusion process, while CTCF modulates this process. We further demonstrate that spatial compartmentalization of the genome is established by an independent process. Recent single-nucleus Hi-C [5,6] allows examining chromosome structure in individual cells and provides additional support for the loop extrusion by cohesin. I will further present most recent results [7] which show that loop extrusion by condensin I and II, can lead to formation of an array of nested loops that, when modeled in 3D, reproduces temporal changes in Hi-C maps during mitotic chromosome compaction.
1. Fudenberg G, Imakaev M, et al Formation of Chromosomal Domains by Loop Extrusion. Cell Rep 15(9) (2016)
2. Goloborodko A, Imakaev MV, Marko JF, Mirny L. Compaction and segregation of sister chromatids via active loop extrusion. Elife 18;5 (2016)
3. Nora EP, et al Targeted degradation of CTCF decouples local insulation of chromosome domains from higher-order genomic compartmentalization http://biorxiv.org/content/early/2017/01/07/095802, Cell (2017) May 18;169(5):930-944
4. Schwarzer W, Goloborodko A., et al. Two independent modes of chromosome organization are revealed by cohesin removal http://biorxiv.org/content/early/2016/12/21/095802, Nature (2017) in press
5. Flyamer IM, Gassler J, Imakaev M, et al., Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition, Nature, 544(7648) (2017)
6. Gassler J, Brandao HB, Imakaev M, Flyamer IM, Ladstatter S, Bickmore WA, Peters JM, Mirny LA, Tachibana-Konwalski K. A Mechanism of Cohesin-Dependent Loop Extrusion Organizes Zygotic Genome Architecture http://www.biorxiv.org/content/early/2017/08/17/177766
7. Gibcus J, Samejima K, Goloborodko A, et al., Mitotic chromosomes fold by condensin-dependent helical winding of chromatin loop arrays http://www.biorxiv.org/content/early/2017/08/10/174649
