Msx3 protein recruits histone deacetylase to down-regulate the Msx1 promoter

R. Mehra-Chaudhary, H. Matsui, Rajendra Raghow

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Msx1 promoter is known to be repressed by Msx1 protein [Shetty, Takahashi, Matsui, Iyengar and Raghow (1999) Biochem. J. 339, 751-758]. We show that in the transiently transfected C2C12 myoblasts, co-expression of Msx3 also causes potent repression of Msx1 promoter that can be relieved by exogenous expression of cAMP-response-element-binding protein-binding protein (CBP) and p300 in a dose-dependent manner. Co-immunoprecipitation and Western blot analyses revealed that Msx3 interacts with CBP and p300 and this interaction significantly decreases the histone acetyltransferase (HAT) activity of both proteins. We also discovered that Msx3-mediated repression of Msx1 promoter is synergized by the exogenous co-expression of histone deacetylase 1 (HDAC1). Furthermore, the repression of Msx1 promoter by Msx3 could be relieved by treating transfected cells with trichostatin A, an inhibitor of HDAC(s). Finally, we show that Msx3 and HDAC1 can be co-immunoprecipitated in a complex that does not contain CBP and that Msx3 and HDAC1 proteins are co-localized in the nucleus. Taken together, our results strongly suggest that two distinct multiprotein complexes are present within the nuclei of C2C12 cells: one containing Msx3 and HDAC(s) and another containing Msx3 and CBP and/or p300. On the basis of these results, we propose a dual mechanism of repression by Msx3 protein that involves the squelching of the HAT activity of co-activators, CBP and p300, and recruitment of HDAC(s).

Original languageEnglish (US)
Pages (from-to)13-22
Number of pages10
JournalBiochemical Journal
Volume353
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Fingerprint

Histone Deacetylases
Histone Deacetylase 1
Down-Regulation
Histone Acetyltransferases
trichostatin A
Proteins
Multiprotein Complexes
Cyclic AMP Response Element-Binding Protein
Histone Deacetylase Inhibitors
Myoblasts
Cell Nucleus
Immunoprecipitation
Protein Binding
Carrier Proteins
Western Blotting

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Msx3 protein recruits histone deacetylase to down-regulate the Msx1 promoter. / Mehra-Chaudhary, R.; Matsui, H.; Raghow, Rajendra.

In: Biochemical Journal, Vol. 353, No. 1, 01.01.2001, p. 13-22.

Research output: Contribution to journalArticle

Mehra-Chaudhary, R. ; Matsui, H. ; Raghow, Rajendra. / Msx3 protein recruits histone deacetylase to down-regulate the Msx1 promoter. In: Biochemical Journal. 2001 ; Vol. 353, No. 1. pp. 13-22.
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