CoREST

A functional corepressor required for regulation of neural- specific gene expression

M. E. Andres, C. Burger, M. J. Peral-Rubio, E. Battaglioli, M. E. Anderson, J. Grimes, J. Dallman, N. Ballas, Gail Mandel

Research output: Contribution to journalArticle

309 Citations (Scopus)

Abstract

Several genes encoding proteins critical to the neuronal phenotype, such as the brain type II sodium channel gene, are expressed to high levels only in neurons. This cell specificity is due, in part, to long-term repression in nonneural cells mediated by the repressor protein REST/NRSF (RE1 silencing transcription factor/neural-restrictive silencing factor). We show here that CoREST, a newly identified human protein, functions as a corepressor for REST. A single zinc finger motif in REST is required for CoREST interaction. Mutations of the motif that disrupt binding also abrogate repression. When fused to a Gal4 DNA-binding domain, CoREST functions as a repressor. CoREST is present in cell lines that express REST, and the proteins are found in the same immunocomplex. CoREST contains two SANT (SW13/ADA2/NCoR/TFIIIB B) domains, a structural feature of the nuclear receptor and silencing mediator for retinoid and thyroid human receptors (SMRT)-extended corepressors that mediate inducible repression by steroid hormone receptors. Together, REST and CoREST mediate repression of the type II sodium channel promoter in nonneural cells, and the REST/CoREST complex may mediate long-term repression essential to maintenance of cell identity.

Original languageEnglish (US)
Pages (from-to)9873-9878
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number17
DOIs
StatePublished - Aug 17 1999
Externally publishedYes

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Co-Repressor Proteins
Gene Expression
Sodium Channels
Nuclear Receptor Co-Repressor 2
Transcription Factor TFIIIB
Repressor Proteins
Proteins
Steroid Receptors
Zinc Fingers
Retinoids
Cytoplasmic and Nuclear Receptors
Thyroid Gland
Maintenance
Hormones
Phenotype
Neurons
Cell Line
Mutation
DNA
Brain

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

CoREST : A functional corepressor required for regulation of neural- specific gene expression. / Andres, M. E.; Burger, C.; Peral-Rubio, M. J.; Battaglioli, E.; Anderson, M. E.; Grimes, J.; Dallman, J.; Ballas, N.; Mandel, Gail.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 17, 17.08.1999, p. 9873-9878.

Research output: Contribution to journalArticle

Andres, M. E. ; Burger, C. ; Peral-Rubio, M. J. ; Battaglioli, E. ; Anderson, M. E. ; Grimes, J. ; Dallman, J. ; Ballas, N. ; Mandel, Gail. / CoREST : A functional corepressor required for regulation of neural- specific gene expression. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 17. pp. 9873-9878.
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