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PMID: 20033039 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes.

Nature ·Vol. 462 ·No. 7276 ·2009-12-24 ·Pages 1016-21

Racki LR, Yang JG, Naber N, Partensky PD, Acevedo A, Purcell TJ, Cooke R, Cheng Y, Narlikar GJ

Abstract

Evenly spaced nucleosomes directly correlate with condensed chromatin and gene silencing. The ATP-dependent chromatin assembly factor (ACF) forms such structures in vitro and is required for silencing in vivo. ACF generates and maintains nucleosome spacing by constantly moving a nucleosome towards the longer flanking DNA faster than the shorter flanking DNA. How the enzyme rapidly moves back and forth between both sides of a nucleosome to accomplish bidirectional movement is unknown. Here we show that nucleosome movement depends cooperatively on two ACF molecules, indicating that ACF functions as a dimer of ATPases. Further, the nucleotide state determines whether the dimer closely engages one or both sides of the nucleosome. Three-dimensional reconstruction by single-particle electron microscopy of the ATPase-nucleosome complex in an activated ATP state reveals a dimer architecture in which the two ATPases face each other. Our results indicate a model in which the two ATPases work in a coordinated manner, taking turns to engage either side of a nucleosome, thereby allowing processive bidirectional movement. This novel dimeric motor mechanism differs from that of dimeric motors such as kinesin and dimeric helicases that processively translocate unidirectionally and reflects the unique challenges faced by motors that move nucleosomes.

MeSH Terms
Adenosine Triphosphatases/metabolism Adenosine Triphosphate/metabolism Animals Cell Line Chromatin Assembly and Disassembly/physiology Chromosomal Proteins, Non-Histone Dimerization Gene Silencing/physiology Histones/metabolism Humans Microscopy, Electron, Transmission Models, Molecular Multiprotein Complexes/metabolism Nucleosomes/chemistry,metabolism Protein Binding Protein Structure, Tertiary Transcription Factors/chemistry,metabolism
Chemicals
BAZ1A protein, human Chromosomal Proteins, Non-Histone Histones Multiprotein Complexes Nucleosomes Transcription Factors Adenosine Triphosphate Adenosine Triphosphatases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Racki Lisa R
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.
Yang Janet G
Naber Nariman
Partensky Peretz D
Acevedo Ashley
Purcell Thomas J
Cooke Roger
Cheng Yifan
Narlikar Geeta J
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
Published
2009-12-24
Pages
1016-21
Language
English
Region
England
NLM ID
0410462
PMCID
PMC2869534
Subset
IM
Grants
NIGMS NIH HHS · R01 GM073767-04 · United States
NIGMS NIH HHS · R01 GM073767-03 · United States
NIGMS NIH HHS · R01 GM073767-02 · United States
NIGMS NIH HHS · R01 GM073767-05 · United States
NIGMS NIH HHS · R01 GM073767-03S1 · United States
NIGMS NIH HHS · R01 GM073767-01 · United States
NIGMS NIH HHS · R01 GM073767 · United States
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