title: The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex.
abstract: The repressor REST/NRSF restricts expression of a large set of genes to neurons by suppressing their expression in non-neural tissues. We find that REST repression involves two distinct repressor proteins. One of these, CoREST, interacts with the COOH-terminal repressor domain of REST (Andres, M. E., Burger, C., Peral-Rubio, M. J., Battaglioli, E., Anderson, M. E., Grimes, J., Dallmanm J., Ballas, N. , and Mandel, G. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 9873-9878). Here we show that the co-repressor mSin3A also interacts with REST. The REST-mSin3A association involves the NH(2)-terminal repressor domain of REST and the paired amphipathic helix 2 domain of mSin3A. REST forms complexes with endogenous mSin3A in mammalian cells, and both mSin3A and CoREST interact with REST in intact mammalian cells. REST repression is blocked in yeast lacking Sin3 and rescued in its presence. In mammalian cells, repression by REST is reduced when binding to mSin3A is inhibited. In mouse embryos, the distribution of mSin3A and REST transcripts is largely coincident. The pattern of CoREST gene expression is more restricted, suggesting that mSin3A is required constitutively for REST repression, whereas CoREST is recruited for more specialized repressor functions.
authors.affiliation: Howard Hughes Medical Institute and Department of Neurobiology and Behavior, State University of New York, Stony Brook, New York, 11794-5230, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Grimes
authors.forename: S J
authors.initials: SJ
authors.lastname: Nielsen
authors.forename: E
authors.initials: E
authors.lastname: Battaglioli
authors.forename: E A
authors.initials: EA
authors.lastname: Miska
authors.forename: J C
authors.initials: JC
authors.lastname: Speh
authors.forename: D L
authors.initials: DL
authors.lastname: Berry
authors.forename: F
authors.initials: F
authors.lastname: Atouf
authors.forename: B C
authors.initials: BC
authors.lastname: Holdener
authors.forename: G
authors.initials: G
authors.lastname: Mandel
authors.forename: T
authors.initials: T
authors.lastname: Kouzarides
mesh_terms: D000818:Animals; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D019084:Fluorescent Antibody Technique, Indirect; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques; D000099229:RE1-Silencing Transcription Factor
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C485650:Rcor2 protein, mouse; C099683:SIN3A transcription factor