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Condensin-dependent chromatin condensation represses transcription globally during quiescence

Sarah G. Swygert, Seungsoo Kim, Xiaoying Wu, Tianhong Fu, Tsung-Han Hsieh, Oliver J. Rando, Robert N. Eisenman, Jay Shendure, Jeffrey N. McKnight, View ORCID ProfileToshio Tsukiyama
doi: https://doi.org/10.1101/320895
Sarah G. Swygert
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA
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Seungsoo Kim
2Genome Sciences, University of Washington, Seattle WA, 98195, USA
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Xiaoying Wu
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA
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Tianhong Fu
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA
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Tsung-Han Hsieh
3Biochemistry and Molecular Pharmacology, University of Massachusetts, Worcester MA 01605, USA
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Oliver J. Rando
3Biochemistry and Molecular Pharmacology, University of Massachusetts, Worcester MA 01605, USA
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Robert N. Eisenman
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA
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Jay Shendure
2Genome Sciences, University of Washington, Seattle WA, 98195, USA
4Howard Hughes Medical Institute, Seattle WA 98195, USA
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Jeffrey N. McKnight
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA
5Present address: Institute of Molecular Biology, University of Oregon, Eugene OR 97403, USA
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Toshio Tsukiyama
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA
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  • ORCID record for Toshio Tsukiyama
  • For correspondence: ttsukiya@fredhutch.org
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SUMMARY

Quiescence is a stress-resistant state in which cells reversibly exit the mitotic cell cycle and suspend most cellular processes. Quiescence is essential for stem cell maintenance and its misregulation is implicated in tumor formation. One of the conserved hallmarks of quiescent cells, from Saccharomyces cerevisiae to humans, is highly condensed chromatin. Here, we use Micro-C XL to map chromatin contacts at single-nucleosome resolution genome-wide to elucidate mechanisms and functions of condensed chromatin in quiescent S. cerevisiae cells. We describe previously uncharacterized chromatin domains on the order of 10-60 kilobases that in quiescent cells are formed by condensin-mediated chromatin loops. Conditional depletion of condensin prevents chromatin condensation during quiescence entry and leads to widespread transcriptional de-repression. We further demonstrate that condensin-dependent chromatin compaction is conserved in quiescent human fibroblasts. We propose that condensin-dependent condensation of chromatin represses transcription throughout the quiescent cell genome.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 14, 2018.
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Condensin-dependent chromatin condensation represses transcription globally during quiescence
Sarah G. Swygert, Seungsoo Kim, Xiaoying Wu, Tianhong Fu, Tsung-Han Hsieh, Oliver J. Rando, Robert N. Eisenman, Jay Shendure, Jeffrey N. McKnight, Toshio Tsukiyama
bioRxiv 320895; doi: https://doi.org/10.1101/320895
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Condensin-dependent chromatin condensation represses transcription globally during quiescence
Sarah G. Swygert, Seungsoo Kim, Xiaoying Wu, Tianhong Fu, Tsung-Han Hsieh, Oliver J. Rando, Robert N. Eisenman, Jay Shendure, Jeffrey N. McKnight, Toshio Tsukiyama
bioRxiv 320895; doi: https://doi.org/10.1101/320895

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