Integrated molecular mechanism directing nucleosome reorganization by human FACT

  1. Kosuke Morikawa3,4
  1. 1Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Sakyo-ku, Kyoto 606-8501, Japan;
  2. 2Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan;
  3. 3Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-konoemachi, Sakyo-ku, Kyoto 606-8501, Japan;
  4. 4International Institute for Advanced Studies, Kizugawa-shi, Kyoto 619-0225, Japan;
  5. 5Department of Biotechnology, Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan;
  6. 6Department of Developmental Genetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan
  1. Corresponding authors: tsunaka.yasuo.3r{at}kyoto-u.ac.jp, morikawa.kosuke.2x{at}kyoto-u.ac.jp

Abstract

Facilitates chromatin transcription (FACT) plays essential roles in chromatin remodeling during DNA transcription, replication, and repair. Our structural and biochemical studies of human FACT–histone interactions present precise views of nucleosome reorganization, conducted by the FACT-SPT16 (suppressor of Ty 16) Mid domain and its adjacent acidic AID segment. AID accesses the H2B N-terminal basic region exposed by partial unwrapping of the nucleosomal DNA, thereby triggering the invasion of FACT into the nucleosome. The crystal structure of the Mid domain complexed with an H3–H4 tetramer exhibits two separate contact sites; the Mid domain forms a novel intermolecular β structure with H4. At the other site, the Mid–H2A steric collision on the H2A-docking surface of the H3–H4 tetramer within the nucleosome induces H2A–H2B displacement. This integrated mechanism results in disrupting the H3 αN helix, which is essential for retaining the nucleosomal DNA ends, and hence facilitates DNA stripping from histone.

Keywords

Footnotes

  • Supplemental material is available for this article.

  • Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.274183.115.

  • Freely available online through the Genes & Development Open Access option.

  • Received October 30, 2015.
  • Accepted February 5, 2016.

This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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