Myocyte enhancer factor 2 (MEF2)-binding site is required for GLUT4 gene expression in transgenic mice: Regulation of MEF2 DNA binding activity in insulin-deficient diabetes

Martin V. Thai, Suresh Guruswamy, Kim T. Cao, Jeffrey E. Pessin, Ann Louise Olson

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

We have previously demonstrated that important regulatory elements responsible for regulated expression of the human GLUT4 promoter are located between -1154 and -412 relative to transcription initiation (Olson, A. L., and Pessin, J. E. (1995) J. Biol. Chem. 270, 23491-23495). Through further analysis of this promoter regulatory region, we have identified a perfectly conserved myocyte enhancer factor 2 (MEF2)-binding domain (-CTAAAAATAG-) that is necessary, but not sufficient, to support tissue-specific expression of a chloramphenicol acetyltransferase reporter gene in transgenic mice. Biochemical analysis of this DNA element demonstrated the formation of a specific DNA-protein complex using nuclear extracts isolated from heart, hindquarter skeletal muscle, and adipose tissue but not from liver. DNA binding studies indicated that this element functionally interacted with the MEF2A and/or MEF2C MADS family of DNA binding transcription factors. MEF2 DNA binding activity was substantially reduced in nuclear extracts isolated from both heart and skeletal muscle of diabetic mice, which correlated with decreased transcription rate of the GLUT4 gene. MEF2 binding activity completely recovered to control levels following insulin treatment. Together these data demonstrated that MEF2 binding activity is necessary for regulation of the GLUT4 gone promoter in muscle and adipose tissue.

Original languageEnglish (US)
Pages (from-to)14285-14292
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number23
DOIs
StatePublished - Jun 5 1998
Externally publishedYes

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MEF2 Transcription Factors
Medical problems
Gene expression
Transgenic Mice
Binding Sites
Insulin
Gene Expression
DNA
Muscle
Transcription
Tissue
Adipose Tissue
Skeletal Muscle
Genes
Muscles
Chloramphenicol O-Acetyltransferase
Nucleic Acid Regulatory Sequences
Level control
Reporter Genes
Genetic Promoter Regions

ASJC Scopus subject areas

  • Biochemistry

Cite this

Myocyte enhancer factor 2 (MEF2)-binding site is required for GLUT4 gene expression in transgenic mice : Regulation of MEF2 DNA binding activity in insulin-deficient diabetes. / Thai, Martin V.; Guruswamy, Suresh; Cao, Kim T.; Pessin, Jeffrey E.; Olson, Ann Louise.

In: Journal of Biological Chemistry, Vol. 273, No. 23, 05.06.1998, p. 14285-14292.

Research output: Contribution to journalArticle

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