Intrauterine growth restriction disrupts developmental epigenetics around distal growth hormone response elements on the rat hepatic IGF‐1 gene

• DOI: 10.1096/fj.14-258442
• Publication Date: 2014-12-03T03:28:12Z
• Authors: Qi Fu; Robert A. McKnight; Christopher W. Ca...; Xing Yu; Robert H. Lane; Amber V. Majnik
• Keywords: Intrauterine growth restriction; Chromatin immunoprecipitation; H3K4me3; Genomic Imprinting

Intrauterine growth restriction (IUGR) decreases serum IGF-1 levels. Postnatal expression is transcriptionally regulated by hormone (GH) through response elements (GHREs). We hypothesized that IUGR disrupts the normal developmental maturation of hepatic intron 2 element (IN2GHRE) histone methylation key lysines and DNA methylation. also evaluated a 5' distal weak enhancer (IGF-15'-upstream region element; 5URGHRE) as GHRE specificity control. was induced well-characterized model bilateral uterine artery ligation pregnant rat. Offspring livers were tested at d 0 21. Chromatin immunoprecipitation bisulfite sequencing quantified epigenetic characteristics. found distinct age-related patterns characterize each GHRE. Development increased H3K4 trimethylation (me3) in both GHREs. However, H3K9me3 decreased with age IN2GHRE 5URGHRE. altered pattern H3K4me3 K9me3 around GHREs sex-specific manner Developmental IUGR-induced occurred GHRE-, CpG site-, manner. conclude epigenetics on rat gene.—Fu, Q., McKnight, R. A., Callaway, C. W., Yu, X., Lane, H., Majnik, A. V. gene. FASEB J. 29, 1176-1184 (2015). www.fasebj.org