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Mol Cell. 2018 Jul 19;71(2):284-293.e4. doi: 10.1016/j.molcel.2018.06.020.

Functions of FACT in Breaking the Nucleosome and Maintaining Its Integrity at the Single-Nucleosome Level.

Author information

1
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
2
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
3
National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
4
Department of Physics, National University of Singapore, Singapore 117542, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
5
Howard Hughes Medical Institute/Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA.
6
National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: mingli@iphy.ac.cn.
7
National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China. Electronic address: weili007@iphy.ac.cn.
8
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: liguohong@ibp.ac.cn.

Abstract

The human FACT (facilitates chromatin transcription) complex, composed of two subunits SPT16 (Suppressor of Ty 16) and SSRP1 (Structure-specific recognition protein-1), plays essential roles in nucleosome remodeling. However, the molecular mechanism of FACT reorganizing the nucleosome still remains elusive. In this study, we demonstrate that FACT displays dual functions in destabilizing the nucleosome and maintaining the original histones and nucleosome integrity at the single-nucleosome level. We found that the subunit SSRP1 is responsible for maintenance of nucleosome integrity by holding the H3/H4 tetramer on DNA and promoting the deposition of the H2A/H2B dimer onto the nucleosome. In contrast, the large subunit SPT16 destabilizes the nucleosome structure by displacing the H2A/H2B dimers. Our findings provide mechanistic insights by which the two subunits of FACT coordinate with each other to fulfill its functions and suggest that FACT may play essential roles in preserving the original histones with epigenetic identity during transcription or DNA replication.

KEYWORDS:

FACT complex; SPT16; SSRP1; magnetic tweezers; nucleosome integrity; nucleosome stability; original histone; single nucleosome

PMID:
30029006
DOI:
10.1016/j.molcel.2018.06.020
[Indexed for MEDLINE]
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