Adenovirus E1A inhibits cardiac myocyte-specific gene expression through its amino terminus

Nanette H. Bishopric, Guo Qing Zeng, Barbara Sato, Keith A. Webster

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Adenovirus E1A oncoproteins inhibit muscle-specific gene expression and myogenic differentiation by suppressing the transcriptional activating functions of basic helix-loop-helix proteins. As one approach to identifying cardiac-specific gene regulatory proteins, we analyzed the functional regions of E1A proteins that are required for muscle gene repression in cardiac cells. Myocyte-specific promoters, including the α-actins and α-myosin heavy chain, were selectively and potently inhibited (>90%) by E1A, while the ubiquitously expressed β-actin promoter was only partially (~30%) repressed; endogenous gene expression was also affected. Distinct E1A protein binding sites mediated repression of muscle-specific and ubiquitous actin promoters. E1A-mediated inhibition of β-actin required both an intact binding site for the tumor repressor proteins pRb and p107 and a second E1A domain (residues 15-35). In contrast, cardiac-specific promoter repression required the E1A amine-terminal residues 2-36. The proximal skeletal actin promoter (3' to base pair -153) was a target for repression by E1A. Although E1A binding to p300 was not required for inhibition of either promoter, co- expression of p300 partially reversed E1A-mediated transcriptional repression. We conclude that cardiac-specific and general promoter inhibition by E1A occurs by distinct mechanisms and that cardiac-specific gene expression is modulated by cellular factors interacting with the E1A p300/CBP-binding domain.

Original languageEnglish (US)
Pages (from-to)20584-20594
Number of pages11
JournalJournal of Biological Chemistry
Volume272
Issue number33
DOIs
StatePublished - Aug 15 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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