MEF2B is a component of a smooth muscle-specific complex that binds an A/T-rich element important for smooth muscle myosin heavy chain gene expression

Youichi Katoh, Jeffery D. Molkentin, Vrushank Dave, Eric N. Olson, Muthu Periasamy

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

To understand smooth muscle-specific gene expression, we have focused our studies on the smooth muscle myosin heavy chain (SMHC) gene, a smooth muscle-specific marker. In this study, we demonstrate that the SMHC promoter region (-1594 to -1462 base pairs) containing the A/T-rich element can activate the heterologous thymidine kinase promotor in smooth muscle cells, but not in fibroblasts. Mutations of this A/T-rich element decreased SMHC promoter activity significantly. Both gel mobility shift assays and DNase I footprinting revealed that this region binds to specific protein complexes from smooth muscle nuclear extracts, whereas nuclear extracts form skeletal muscle and fibroblasts produced a different binding pattern. We also demonstrate that the protein complex obtained from smooth muscle nuclear extract reacts with MEF2B-specific antibody, but not with antibodies specific to MEF2A, MEF2C, or MEF2D, suggesting that only MEF2B protein binds to the A/T-rich element. Furthermore, MEF2B overexpression in smooth muscle cells up-regulated the SMHC promoter, suggesting that MEF2B is important for SMHC gene regulation. This is the first report demonstrating a role for MEF2 factors in smooth muscle-specific gene expression.

Original languageEnglish (US)
Pages (from-to)1511-1518
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number3
DOIs
StatePublished - Jan 16 1998

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Smooth Muscle Myosins
Myosin Heavy Chains
Gene expression
Smooth Muscle
Muscle
Gene Expression
Smooth Muscle Myocytes
Fibroblasts
MEF2 Transcription Factors
Thymidine Kinase
Antibodies
Deoxyribonuclease I
Electrophoretic Mobility Shift Assay
Genetic Promoter Regions
Base Pairing
Cells
Genes
Skeletal Muscle
Proteins
Gels

ASJC Scopus subject areas

  • Biochemistry

Cite this

MEF2B is a component of a smooth muscle-specific complex that binds an A/T-rich element important for smooth muscle myosin heavy chain gene expression. / Katoh, Youichi; Molkentin, Jeffery D.; Dave, Vrushank; Olson, Eric N.; Periasamy, Muthu.

In: Journal of Biological Chemistry, Vol. 273, No. 3, 16.01.1998, p. 1511-1518.

Research output: Contribution to journalArticle

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