Myocardial activation of the human cardiac α-actin promoter by helix- loop-helix proteins

V. Sartorelli, N. A. Hong, Nanette Bishopric, L. Kedes

Research output: Contribution to journalArticle

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Abstract

The cardiac α-actin gene is expressed in both heart and skeletal muscle. In skeletal myogenic cells, the 177-base-pair promoter of the human cardiac α-actin (HCA) gene requires three transcription factors for activation: Sp1, serum response factor (SRF), and MyoD. However, MyoD is undetectable in heart. To search for a functional equivalent of MyoD, we analyzed the transcriptional regulation of the HCA promoter in primary cultures of rat cardiac myocytes. The same DNA sequence elements recognized by SRF, Sp1, and MyoD and required for HCA transcription in skeletal muscle cells were also found to be necessary for expression in cardiomyocytes. Overexpression of Id, a negative regulator of basic helix-loop-helix proteins, selectively attenuated expression of the HCA promoter. Cardiomyocyte nuclei contain a protein complex that specifically interacts with the same required sequence (E box) in the HCA promoter that is bound by MyoD in skeletal myogenic cells. Furthermore, these complexes contain a peptide that is a member of the E2A family of basic helix-loop-helix proteins. Cardiomyocyte nuclei appear to be enriched for a protein that can bind to the E-box site as dimers with the E12 protein. These results suggest that a member of the basic helix-loop-helix family, together with SRF and Sp1, activates the HCA promoter in heart. Alternative strategies for myocardial transcription of HCA are discussed.

Original languageEnglish
Pages (from-to)4047-4051
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number9
StatePublished - Jan 1 1992
Externally publishedYes

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Actins
Serum Response Factor
Cardiac Myocytes
Proteins
E-Box Elements
Skeletal Muscle
Base Pairing
Muscle Cells
Transcriptional Activation
Genes
Myocardium
Transcription Factors
Peptides

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Myocardial activation of the human cardiac α-actin promoter by helix- loop-helix proteins. / Sartorelli, V.; Hong, N. A.; Bishopric, Nanette; Kedes, L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 9, 01.01.1992, p. 4047-4051.

Research output: Contribution to journalArticle

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