RE1 silencing transcription factor is involved in regulating neuron-specific expression of alpha-internexin and neurofilament genes.
Alpha-internexin and the neurofilament triplet proteins (NF-L, NF-M, and NF-H) co-assemble into intermediate filament networks in neurons. We have found that the RE1 silencing transcription factor (REST) plays a contributory role in the neuron-specific expression of the alpha-internexin, NF-H and NF-M genes. Chromatin immunoprecipitation and transient transfection experiments performed with catecholaminergic neuronal Cath a.-differentiated (CAD) cells and non-neuronal NIH3T3 cells demonstrated that REST repressed transcription of these genes in NIH3T3 cells by binding and recruiting mSin3A, CoREST, histone deacetylase (HDAC) 1 and MeCP2 to the RE1 sites in the intron-1 of alpha-internexin and the 5' flanking regions of NF-H and NF-M. No repression effect of the RE1 sites was observed in CAD cells, which express these neuronal genes but not REST. Treatment of NIH3T3 cells with trichostatin A, a HDAC inhibitor, relieved the REST-mediated repression and induced ectopic activation of alpha-internexin, NF-H and NF-M. The trichostatin A treatment did not affect the levels of REST occupancy but caused coordinated changes in acetylation and methylation of histones around the RE1 sites of these genes in NIH3T3 cells consistent with a transition from transcriptional repression to transcriptional activation. Thus, REST regulates expression of these neuronal genes, partly by a HDAC-dependent epigenetic mechanism.
Ching
Gee Y
GY
Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Liem
Ronald K H
RK
D000818:Animals; D002460:Cell Line; D047369:Chromatin Immunoprecipitation / Q000379:methods; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014162:Transfection / Q000379:methods; D000099229:RE1-Silencing Transcription Factor
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D007381:Intermediate Filament Proteins; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D012097:Repressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D000099229:RE1-Silencing Transcription Factor; C497393:Mecp2 protein, mouse; C485650:Rcor2 protein, mouse; C099683:SIN3A transcription factor; C046643:alpha-internexin; C484389:Hdac1 protein, mouse