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

Autor: Mekonnen Lemma Dechassa, Arjan Hada, Solomon G. Hailu, Blaine Bartholomew, Sandipan Brahma, Payel Sen, Jie Luo, Jeff Ranish, Somnath Paul, Jim Persinger
Rok vydání: 2016
Předmět:
Zdroj: Cell Reports, Vol 18, Iss 9, Pp 2135-2147 (2017)
ISSN: 2211-1247
Popis: Summary: 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. : Mutation of SWI/SNF chromatin remodeling complex subunits contributes to cancer and neurological disorders. Sen et al. report that loss of the Snf5 subunit alters the architecture and function of SWI/SNF in a yeast model system. These findings may reflect changes that occur in pediatric rhabdoid tumors with mutated Snf5. Keywords: Chromatin remodeling, SWI/SNF, Snf5, SMARCB1, BAF47, INI1
Databáze: OpenAIRE