A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes

Mohamed Ali Hakimi, Daniel A. Bochar, Josh Chenoweth, William S. Lane, Gail Mandel, Ramin Shiekhattar

Research output: Contribution to journalArticlepeer-review

220 Scopus citations

Abstract

BRAF35, a structural DNA-binding protein, initially was identified as a component of a large BRCA2-containing complex. Biochemical analysis revealed the presence of a smaller core-BRAF35 complex devoid of BRCA2. Here we report the isolation of a six-subunit core-BRAF35 complex with the capacity to deacetylate histones, termed the BRAF-histone deacetylase complex (BHC), from human cells. BHC contains polypeptides reminiscent of the chromatin-remodeling complexes SWI/SNF and NuRD (nucleosome remodeling and deacetylating). Similar to NuRD, BHC contains an Mi2-like subunit, BHC80, and a PHD zinc-finger subunit as well as histone deacetylases 1/2 and an MTA-like subunit, the transcriptional corepressor CoREST. We show that BHC mediates repression of neuron-specific genes through the cis-regulatory element known as the repressor element 1 or neural restrictive silencer (RE1/NRS). Chromatin-immunoprecipitation experiments demonstrate the recruitment of BHC by the neuronal repressor REST. Expression of BRAF35 containing a single point mutation in the HMG domain of the protein abrogated REST-mediated transcriptional repression. These results demonstrate a role for core-BRAF35-containing complex in the regulation of neuron-specific genes through modulation of the chromatin structure.

Original languageEnglish (US)
Pages (from-to)7420-7425
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number11
DOIs
StatePublished - May 28 2002
Externally publishedYes

ASJC Scopus subject areas

  • General

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