Seminars – Genome in 3D: models of chromosome folding

EVENT : C3BI Seminars

Genome in 3D: models of chromosome folding

Main speaker : Leonid Mirny, from Professor of Institute for Medical Engineering and Science and Physics. Harvard-MIT Division of Health Sciences and Technology, MIT, USA
Date : 23/11/2017 at 02:00 pm
Location : Retrovirus room – LWOFF (22) ,Institut Pasteur, Paris

DNA of the human genome is 2m long and is folded into chromosomes that fit in 10-micron cellular nucleus. How are these long polymers of DNA folded and organized in 3D inside the nucleus? How can proteins that are much smaller than chromosomes drive chromosome compaction, segregation or control functional interactions at much larger scales? Recently developed Chromosome Conformation Capture technique (Hi-C) provides comprehensive information about frequencies of spatial interactions between genomic loci. Inferring principles and mechanisms of 3D organization of chromosomes from these and imaging data is a challenging biophysical problem. Recently we proposed that chromosomes are organized by an active, motor-driven process of loop extrusion. Loop extrusion can be a universal mechanism responsible for formation of domains and facilitation on enhancer-promoter interaction during interphase [1], and chromosome compaction and segregation in metaphase [2]. I will review recent experimental studies [3-5] that provide strong support to loop extrusion as a universal mechanism of chromosome folding.

1. Fudenberg G, Imakaev M, Lu C, Goloborodko A, Abdennur N, Mirny LA. Formation of Chromosomal Domains by Loop Extrusion. Cell Rep. 15(9):2038-49 (2016) 2. Goloborodko A, Imakaev MV, Marko JF, Mirny L. Compaction and segregation of sister chromatids via active loop extrusion. Elife. May 18;5 (2016) 3. Nora EP, Goloborodko A, Valton A-L , Gibcus J , Uebersohn A, Abdennur N , Dekker J , Mirny LA , Bruneau BG Targeted degradation of CTCF decouples local insulation of chromosome domains from higher-order genomic compartmentalization Cell May 18, 169:5 (2017) 4. Schwarzer W, Abdennur N, Goloborodko A, Pekowska A , Fudenberg G , Loe-Mie Y, Fonseca NA , Huber W , Haering C, Mirny LA, Spitz F Two independent modes of chromosome organization are revealed by cohesin removal Nature Sept 27 (2017) 5. Gibcus J, Samejima K, Goloborodko A, et al., Mitotic chromosomes fold by condensin-dependent helical winding of chromatin loop arrays (2017)

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