Role of myocyte-specific enhancer-binding factor (MEF-2) in transcriptional regulation of the α-cardiac myosin heavy chain gene

Eric A. Adolph, Arun Subramaniam, Peter Cserjesi, Eric N. Olson, Jeffrey Robbins

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The intergenic region between the mouse α-cardiac myosin heavy chain and β-myosin heavy chain genes has previously been shown to direct expression of the bacterial chloramphenicol acetyltransferase reporter gene in transgenic mice in a tissue-specific manner. Sequence analyses located a putative myocyte-specific enhancer-binding factor (MEF-2) site situated in the regulatory region of this gene proximal to the start site of transcription. The role of this element in directing the cardiac compartment-specific expression of the transgene was assessed. The polymerase chain reaction was used to perform substitution mutagenesis of the MEF-2 binding site, and lack of MEF-2 binding was confirmed by gel retardation assays. The resultant construct was used to generate transgenic mice. Surprisingly, transgene expression was not down-regulated, but was significantly increased in the hearts of the MEF-2 mutant mice. In addition, cardiac-specific expression of the transgene was perturbed with significant levels of ectopic expression occurring in the aorta.

Original languageEnglish (US)
Pages (from-to)5349-5352
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number8
StatePublished - Mar 15 1993

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MEF2 Transcription Factors
Cardiac Myosins
Myosin Heavy Chains
Transgenes
Genes
Transgenic Mice
Mutagenesis
Intergenic DNA
Chloramphenicol O-Acetyltransferase
Nucleic Acid Regulatory Sequences
Transcription Initiation Site
Polymerase chain reaction
Electrophoretic Mobility Shift Assay
Regulator Genes
Reporter Genes
Sequence Analysis
Aorta
Assays
Substitution reactions
Gels

ASJC Scopus subject areas

  • Biochemistry

Cite this

Role of myocyte-specific enhancer-binding factor (MEF-2) in transcriptional regulation of the α-cardiac myosin heavy chain gene. / Adolph, Eric A.; Subramaniam, Arun; Cserjesi, Peter; Olson, Eric N.; Robbins, Jeffrey.

In: Journal of Biological Chemistry, Vol. 268, No. 8, 15.03.1993, p. 5349-5352.

Research output: Contribution to journalArticle

Adolph, Eric A. ; Subramaniam, Arun ; Cserjesi, Peter ; Olson, Eric N. ; Robbins, Jeffrey. / Role of myocyte-specific enhancer-binding factor (MEF-2) in transcriptional regulation of the α-cardiac myosin heavy chain gene. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 8. pp. 5349-5352.
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