We examined transcriptional and epigenetic mechanism(s) behind diminished skeletal muscle (SM) GLUT4 mRNA in intra-uterine 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 (CON) 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 methyl transferase 1 (DNMT1) in postnatal, DNMT3a and DNMT3b in adult were differentially recruited with increased methyl CpG binding protein (MeCP) 2 concentrations, to bind the IUGR GLUT4 gene. Co-valent modifications of the histone (H) code consisted of H3.K14 de-acetylation by recruitment of histone deacetylase 1 (HDAC1) and enhanced association of HDAC4 enzymes. This set the stage for Suv39H1 methylase mediated di-methylation of H3.K9 and increased recruitment of heterochromatin protein 1, that partially inactivate postnatal and adult IUGR GLUT4 gene transcription. Further increased interaction in the adult IUGR between DNMT3a/DNMT3b and HDAC1, MEF2D and HDAC1/HDAC4 but decreased association between MyoD and MEF2A existed. We conclude that epigenetic mechanisms consisting of histone code modifications repress SM GLUT4 transcription in the postnatal persisting in the adult female IUGR offspring.