Control of Cardiac-specific Transcription by p300 through Myocyte Enhancer Factor-2D

Tatiana I. Slepak, Keith A. Webster, Jie Zang, Howard Prentice, Ann O'Dowd, Martin N. Hicks, Nanette H. Bishopric

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

The transcriptional integrator p300 regulates gene expression by interaction with sequence-specific DNA-binding proteins and local remodeling of chromatin. p300 is required for cardiac-specific gene transcription, but the molecular basis of this requirement is unknown. Here we report that the MADS (MCM-1, agamous, deficiens, serum response factor) box transcription factor myocyte enhancer factor-2D (MEF-2D) acts as the principal conduit for cardiac transcriptional activation by p300. p300 activation of the native 2130-base pair human skeletal α-actin promoter required a single hybrid MEF-2/ GATA-4 DNA motif centered at - 1256 base pairs. Maximal expression of the promoter in cultured myocytes and in vivo correlated with binding of both MEF-2 and p300, but not GATA-4, to this AT-rich motif. p300 and MEF-2 were coprecipitated from cardiac nuclear extracts by an oligomer containing this element. p300 was found exclusively in a complex with MEF-2D at this and related sites in other cardiac-restricted promoters. MEF-2D, but not other MEFs, significantly potentiated cardiac-specific transcription by p300. No physical or functional interaction was observed between p300 and other factors implicated in skeletal actin transcription, including GATA-4, TEF-1, or SRF. These results show that, in the intact cell, p300 interactions with its protein targets are highly selective and that MEF-2D is the preferred channel for p300-mediated transcriptional control in the heart.

Original languageEnglish (US)
Pages (from-to)7575-7585
Number of pages11
JournalJournal of Biological Chemistry
Volume276
Issue number10
DOIs
StatePublished - Mar 9 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Slepak, T. I., Webster, K. A., Zang, J., Prentice, H., O'Dowd, A., Hicks, M. N., & Bishopric, N. H. (2001). Control of Cardiac-specific Transcription by p300 through Myocyte Enhancer Factor-2D. Journal of Biological Chemistry, 276(10), 7575-7585. https://doi.org/10.1074/jbc.M004625200