Loss of Snf5 Induces Formation of an Aberrant SWI/SNF Complex.

Autor: Sen P; Department of Biochemistry and Molecular Biology, Southern Illinois University, Carbondale, IL 62901, USA., Luo J; Institute for Systems Biology, Seattle, WA 98109, USA., Hada A; UT MD Anderson Cancer Center, Smithville, TX 78597, USA; UT MD Anderson Center for Cancer Epigenetics, Smithville, TX 78597, USA., Hailu SG; UT MD Anderson Cancer Center, Smithville, TX 78597, USA; UT MD Anderson Center for Cancer Epigenetics, Smithville, TX 78597, USA., Dechassa ML; Department of Biochemistry and Molecular Biology, Southern Illinois University, Carbondale, IL 62901, USA., Persinger J; UT MD Anderson Cancer Center, Smithville, TX 78597, USA; UT MD Anderson Center for Cancer Epigenetics, Smithville, TX 78597, USA., Brahma S; UT MD Anderson Cancer Center, Smithville, TX 78597, USA., Paul S; UT MD Anderson Cancer Center, Smithville, TX 78597, USA., Ranish J; Institute for Systems Biology, Seattle, WA 98109, USA., Bartholomew B; UT MD Anderson Cancer Center, Smithville, TX 78597, USA; UT MD Anderson Center for Cancer Epigenetics, Smithville, TX 78597, USA. Electronic address: bbartholomew@mdanderson.org.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2017 Feb 28; Vol. 18 (9), pp. 2135-2147.
DOI: 10.1016/j.celrep.2017.02.017
Abstrakt: The SWI/SNF chromatin remodeling complex is highly conserved from yeast to human, and aberrant SWI/SNF complexes contribute to human disease. The Snf5/SMARCB1/INI1 subunit of SWI/SNF is a tumor suppressor frequently lost in pediatric rhabdoid cancers. We examined the effects of Snf5 loss on the composition, nucleosome binding, recruitment, and remodeling activities of yeast SWI/SNF. The Snf5 subunit is shown by crosslinking-mass spectrometry (CX-MS) and subunit deletion analysis to interact with the ATPase domain of Snf2 and to form a submodule consisting of Snf5, Swp82, and Taf14. Snf5 promotes binding of the Snf2 ATPase domain to nucleosomal DNA and enhances the catalytic and nucleosome remodeling activities of SWI/SNF. Snf5 is also required for SWI/SNF recruitment by acidic transcription factors. RNA-seq analysis suggests that both the recruitment and remodeling functions of Snf5 are required in vivo for SWI/SNF regulation of gene expression. Thus, loss of SNF5 alters the structure and function of SWI/SNF.
(Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE