REST repression of neuronal genes requires components of the hSWI.SNF complex

J Biol Chem. 2002 Oct 25;277(43):41038-45. doi: 10.1074/jbc.M205691200. Epub 2002 Aug 20.

Abstract

A function of the transcription factor REST is to block the expression of neuronal phenotypic traits in non-neuronal cells. Previous studies have shown that REST-mediated repression requires histone deacetylase activity and that recruitment of deacetylases is mediated by two co-repressors, Sin3A and CoREST. In this study, we show that a repressor domain in CoREST interacts with BRG1-associated factor (BAF) 57, a component of the hSWI.SNF complex. In vivo, BAF57 occupies the neuronal sodium channel gene (Nav1.2) promoter, and targeting to this gene requires REST. In addition to BAF57, the ATPase BRG1 and BAF170, other members of the hSWI.SNF complex, are also present in the REST.CoREST repressor complex. Microinjection of specific antibodies against BRG1, BAF57, or BAF170 into Rat1 fibroblasts relieves repression of RE1 reporter genes. Together, our data suggest that ATP-dependent chromatin remodeling, as well as histone deacetylation, is needed for REST-mediated repression.

Publication types

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

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomal Proteins, Non-Histone / physiology*
  • Gene Expression Regulation / physiology*
  • Histone Deacetylases / metabolism
  • Humans
  • Molecular Sequence Data
  • NAV1.2 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / genetics
  • Neurons / enzymology
  • Neurons / metabolism*
  • Promoter Regions, Genetic
  • Rats
  • Repressor Proteins / metabolism
  • Repressor Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Sodium Channels / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Two-Hybrid System Techniques

Substances

  • Chromosomal Proteins, Non-Histone
  • NAV1.2 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • RE1-silencing transcription factor
  • Repressor Proteins
  • SCN2A protein, human
  • SWI-SNF-B chromatin-remodeling complex
  • Scn2A protein, rat
  • Scn2a protein, mouse
  • Smarce1 protein, mouse
  • Sodium Channels
  • Transcription Factors
  • Histone Deacetylases