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PMID: 1850096 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governing myogenic induction of the avian cardiac alpha-actin promoter.

Molecular and cellular biology ·Vol. 11 ·No. 5 ·1991-05-00 ·Pages 2439-50

French BA, Chow KL, Olson EN, Schwartz RJ

Abstract

Recent studies have shown that two genes regulating myogenesis (MyoD and myogenin) are coexpressed with cardiac alpha-actin during early stages of skeletal muscle development. Myogenin and MyoD are members of a family of regulatory proteins which share a helix-loop-helix (HLH) motif required for dimerization and DNA binding. Myogenin and MyoD form heterodimers with the ubiquitous HLH protein E12 which bind cis-acting DNA elements that have an E box (CANNTG) at their core. E boxes are present in the control regions of numerous muscle-specific genes, although their functional importance in regulating many of these genes has not yet been evaluated. In this report we examine the possibility that myogenin (or MyoD) directly transactivates the cardiac alpha-actin promoter. Heterodimers of myogenin and E12 (or MyoD and E12) specifically bound a restriction fragment extending from -200 to -103 relative to the start of cardiac alpha-actin transcription. Methylation interference footprints pinpointed the site of interaction to an E box immediately adjacent to a previously identified CArG box (CArG3). Site-directed mutations to the DNA-binding site revealed that either an intact E box or an intact CArG3 is required for induction of the cardiac alpha-actin promoter in myoblasts and for transactivation by myogenin in cotransfected fibroblasts. However, deletion and substitution experiments indicate that the complex E box/CArG3 element alone does not confer muscle-specific expression to a minimal promoter. These results suggest that direct and indirect pathways involving multiple cis-acting elements mediate the induction of the cardiac alpha-actin promoter by myogenin and MyoD.

MeSH Terms
Actins/genetics Animals Base Sequence Cell Line Cells, Cultured Chick Embryo DNA/genetics,metabolism DNA-Binding Proteins/genetics Macromolecular Substances Methylation Mice Molecular Sequence Data Muscle Proteins/genetics,metabolism Muscles/metabolism Mutagenesis, Site-Directed MyoD Protein Myocardium/metabolism Myogenin Oligonucleotide Probes Plasmids Promoter Regions, Genetic Protein Biosynthesis Restriction Mapping Trans-Activators/genetics Transcription, Genetic Transfection
Chemicals
Actins DNA-Binding Proteins Macromolecular Substances Muscle Proteins MyoD Protein Myog protein, mouse Myogenin Oligonucleotide Probes Trans-Activators DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
French B A
Department of Cell Biology, Baylor College of Medicine, Houston, Texas.
Chow K L
Olson E N
Schwartz R J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.11.5.2439-2450.1991
Published
1991-05-00
Pages
2439-50
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360005
Subset
IM
Grants
NHLBI NIH HHS · HL38401 · United States
External Links
PubMed source DOI: 10.1128/mcb.11.5.2439-2450.1991 PMC Full Text View journal details
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