REST repression of neuronal genes requires components of the hSWI.SNF complex.
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.
Department of Neurobiology and Behavior, Howard Hughes Medical Institute, State University of New York, Stony Brook, NY 11794, USA.
Elena
E
Battaglioli
Maria E
ME
Andrés
Dave W
DW
Rose
Josh G
JG
Chenoweth
Michael G
MG
Rosenfeld
Mary E
ME
Anderson
Gail
G
Mandel
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D000099229:RE1-Silencing Transcription Factor
D002868:Chromosomal Proteins, Non-Histone; D006655:Histone Deacetylases; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D015222:Sodium Channels; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C568251:SCN2A protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; C568253:Scn2A protein, rat; C000654500:Scn2a protein, mouse; C465207:Smarce1 protein, mouse