The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex

Julia A. Grimes, Søren J. Nielsen, Elena Battaglioli, Eric A. Miska, Joan C. Speh, Dianna L. Berry, Fouad Atouf, Bernadette C. Holdener, Gail Mandel, Tony Kouzarides

Research output: Contribution to journalArticle

172 Citations (Scopus)

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 NH2-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.

Original languageEnglish (US)
Pages (from-to)9461-9467
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number13
DOIs
StatePublished - Mar 31 2000
Externally publishedYes

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Co-Repressor Proteins
Cells
Repressor Proteins
Gene expression
Yeast
Neurons
Embryonic Structures
Genes
Yeasts
Tissue
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

Grimes, J. A., Nielsen, S. J., Battaglioli, E., Miska, E. A., Speh, J. C., Berry, D. L., ... Kouzarides, T. (2000). The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex. Journal of Biological Chemistry, 275(13), 9461-9467. https://doi.org/10.1074/jbc.275.13.9461

The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex. / Grimes, Julia A.; Nielsen, Søren J.; Battaglioli, Elena; Miska, Eric A.; Speh, Joan C.; Berry, Dianna L.; Atouf, Fouad; Holdener, Bernadette C.; Mandel, Gail; Kouzarides, Tony.

In: Journal of Biological Chemistry, Vol. 275, No. 13, 31.03.2000, p. 9461-9467.

Research output: Contribution to journalArticle

Grimes, JA, Nielsen, SJ, Battaglioli, E, Miska, EA, Speh, JC, Berry, DL, Atouf, F, Holdener, BC, Mandel, G & Kouzarides, T 2000, 'The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex', Journal of Biological Chemistry, vol. 275, no. 13, pp. 9461-9467. https://doi.org/10.1074/jbc.275.13.9461
Grimes JA, Nielsen SJ, Battaglioli E, Miska EA, Speh JC, Berry DL et al. The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex. Journal of Biological Chemistry. 2000 Mar 31;275(13):9461-9467. https://doi.org/10.1074/jbc.275.13.9461
Grimes, Julia A. ; Nielsen, Søren J. ; Battaglioli, Elena ; Miska, Eric A. ; Speh, Joan C. ; Berry, Dianna L. ; Atouf, Fouad ; Holdener, Bernadette C. ; Mandel, Gail ; Kouzarides, Tony. / The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 13. pp. 9461-9467.
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