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Cell Rep. 2017 Feb 28;18(9):2124-2134. doi: 10.1016/j.celrep.2017.01.058.

Composition and Function of Mutant Swi/Snf Complexes.

Author information

1
Department of Cell and Molecular Biology, University of Rhode Island, 120 Flagg Road, Kingston, RI 02881, USA. Electronic address: arnob@uri.edu.
2
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
3
Institute of Cancer Biological Therapy, Xuzhou Medical University, Jiangsu 221002, China.
4
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA; Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
5
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
6
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. Electronic address: jlw@stowers.org.

Abstract

The 12-subunit Swi/Snf chromatin remodeling complex is conserved from yeast to humans. It functions to alter nucleosome positions by either sliding nucleosomes on DNA or evicting histones. Interestingly, 20% of all human cancers carry mutations in subunits of the Swi/Snf complex. Many of these mutations cause protein instability and loss, resulting in partial Swi/Snf complexes. Although several studies have shown that histone acetylation and activator-dependent recruitment of Swi/Snf regulate its function, it is less well understood how subunits regulate stability and function of the complex. Using functional proteomic and genomic approaches, we have assembled the network architecture of yeast Swi/Snf. In addition, we find that subunits of the Swi/Snf complex regulate occupancy of the catalytic subunit Snf2, thereby modulating gene transcription. Our findings have direct bearing on how cancer-causing mutations in orthologous subunits of human Swi/Snf may lead to aberrant regulation of gene expression by this complex.

KEYWORDS:

Snf2 occupancy; Swi/Snf complex; Swi/Snf subunits; architecture; cancer; gene expression; modularity; patterns; residual Swi/Snf complexes; targeting

PMID:
28249159
PMCID:
PMC5837817
DOI:
10.1016/j.celrep.2017.01.058
[Indexed for MEDLINE]
Free PMC Article

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