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

Proc Natl Acad Sci U S A. 2002 May 28;99(11):7420-5. doi: 10.1073/pnas.112008599.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • Chromatin / ultrastructure
  • Chromatography, Ion Exchange
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / pharmacology
  • Gene Expression Regulation / drug effects*
  • HeLa Cells
  • High Mobility Group Proteins
  • Histone Deacetylases / metabolism*
  • Histone Deacetylases / pharmacology
  • Humans
  • Molecular Sequence Data
  • Neurons / physiology*
  • Protein Subunits
  • Repressor Proteins / metabolism*
  • Synapsins / genetics
  • Transcription, Genetic / drug effects*
  • Zinc Fingers

Substances

  • Chromatin
  • DNA-Binding Proteins
  • HMG20B protein, human
  • High Mobility Group Proteins
  • Protein Subunits
  • Repressor Proteins
  • Synapsins
  • Histone Deacetylases

Associated data

  • GENBANK/AY090777