Transcriptional repression by REST: recruitment of Sin3A and histone deacetylase to neuronal genes.
Many genes whose expression is restricted to neurons in the brain contain a silencer element (RE1/NRSE) that limits transcription in nonneuronal cells by binding the transcription factor REST (also named NRSF or XBR). Although two independent domains of REST are known to confer repression, the mechanisms of transcriptional repression by REST remain obscure. We provide multiple lines of evidence that the N-terminal domain of REST represses transcription of the GluR2 and type II sodium-channel genes by recruiting the corepressor Sin3A and histone deacetylase (HDAC) to the promoter region in nonneuronal cells. These results identify a general mechanism for controlling the neuronal expression pattern of a specific set of genes via the RE1 silencer element.
Huang
Y
Y
Department of Pharmacology and Biochemistry, Cell and Developmental Biology Graduate Program, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Myers
S J
SJ
Dingledine
R
R
D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D000099229:RE1-Silencing Transcription Factor
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D018091:Receptors, AMPA; D012097:Repressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C099683:SIN3A transcription factor; C012589:trichostatin A; C104722:glutamate receptor ionotropic, AMPA 2