Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Wednesday Speaker Abstracts

MECHANISMS AND FUNCTIONS OF CHROMATIN CONDENSATION IN QUIESCENT YEAST CELLS Sarah G Swygert 1 ; Seungsoo Kim 2 ; Xiaoying Wu 1 ; Tianhong Fu 1 ; Tsung-Han Hsieh 3 ; Rando Oliver 3 ; Jay Shendure 2 ; Jeffrey McKnight 1 ; Toshio Tsukiyama 1 ; 1 Fred Hutchinson Cancer Research Center, Basic Sciences Division, Seattle, Washington, United States 2 U Washington, Genome Sciences, Seattle, Washington, United States 3 U Massachusetts Medical School, Biochemistry and Pharmacology, Worcester, Massachusetts, United States Eukaryotic cells, from yeast to humans, spend most of their time in quiescence, a state in which cells exist for long periods of time without cycling until receiving external signals to resume division. We have been investigating molecular mechanisms underlying cell quiescence using S. cerevisiae as a model organism. One of the conserved hallmarks of quiescent cells is highly condensed chromatin. However, the molecular mechanisms and biological roles for chromatin condensation in quiescent cells remain unknown in any organism. To address this issue, we have performed Micro-C XL, a nucleosome resolution (200 bp) variant of Hi-C. This revealed that yeast cells have previously unidentified chromatin domains on the order of 10-60 kilobases across the genome. In quiescent cells, condensin binds at the borders of these chromatin domains and facilitates chromatin loop formation and interactions within the domains. Conditional depletion of condensin prevents chromatin condensation during quiescence entry and leads to widespread transcriptional de-repression. Finally, we confirmed that condensin-dependent chromatin compaction is conserved in quiescent human fibroblasts. Biological roles for condensin functions, molecular mechanisms of condensin targeting, and other aspects of chromatin condensation in quiescent cells will be discussed.

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