Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF‐1 gene

Abstract

Intrauterine growth restriction (IUGR) decreases serum insulin growth factor‐1 (IGF‐1) levels. IGF‐1 is an epigenetically regulated gene that has two promoters, alternative exon 5 splicing, and multiple termination sites. The regulation of gene expression involves the whole gene, as evidenced by the aforementioned IGF‐1 paradigm. We hypothesized that IUGR in the rat would affect hepatic IGF‐1 expression and alter the epigenetic characteristics of the IGF‐1 gene along its length. IUGR was induced through a bilateral uterine artery ligation of the pregnant rat, a well‐characterized model of IUGR. Pups from anesthesia and shamoperated dams were used as controls. Real‐time RT‐ PCR and ELISA was used to measure expression at day of life (DOL) 0 and 21. Bisulfite sequencing and chromatin immunoprecipitation (ChIP) quantified IGF‐1 epigenetic characteristics. A nontranscribed intergenic control was used for ChIP studies. IUGR decreased hepatic and serum IGF‐1. Concurrently, IUGR modified epigenetic characteristics, particularly the histone code, along the length of the hepatic IGF‐1 gene. Many changes persisted postnatally, and the postnatal effect of IUGR on the histone code was gender‐specific. We conclude that IUGR modifies epigenetic characteristics of the rat hepatic IGF‐1 gene along the length of the whole gene.— Fu, Q.,Yu, X., Callaway, C. W., Lane, R. H., McKnight, R. A. Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF‐1 gene. FASEBJ. 23, 2438–2449 (2009)