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 Scopus citations

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 - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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