Histone code modifications repress glucose transporter 4 expression in the intrauterine growth-restricted offspring.

ABSTRACT: We examined transcriptional and epigenetic mechanism(s) behind diminished skeletal muscle GLUT4 mRNA in intrauterine growth-restricted (IUGR) female rat offspring. An increase in MEF2D (inhibitor) with a decline in MEF2A (activator) and MyoD (co-activator) binding to the glut4 promoter in IUGR versus control was observed. The functional role of MEF2/MyoD-binding sites and neighboring three CpG clusters in glut4 gene transcription was confirmed in C2C12 muscle cells. No differential methylation of these three and other CpG clusters in the glut4 promoter occurred. DNA methyltransferase 1 (DNMT1) in postnatal, DNMT3a, and DNMT3b in adult was differentially recruited with increased MeCP2 (methyl CpG-binding protein) concentrations to bind the IUGR glut4 gene. Covalent modifications of the hist

SUBMITTER: Raychaudhuri N 

PROVIDER: S-EPMC2376250 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature