Faculty Collaboration Database

Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene. FASEB J 2009 Aug;23(8):2438-49

Date

04/15/2009

Pubmed ID

19364764

Pubmed Central ID

PMC2717764

DOI

10.1096/fj.08-124768

Scopus ID

2-s2.0-68849107606 (requires institutional sign-in at Scopus site)   165 Citations

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 sham-operated 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.

Author List

Fu Q, Yu X, Callaway CW, Lane RH, McKnight RA

MESH terms used to index this publication - Major topics in bold

Alternative Splicing
Animals
Animals, Newborn
Base Sequence
DNA Methylation
DNA Primers
Epigenesis, Genetic
Female
Fetal Growth Retardation
Gene Expression Regulation, Developmental
Histones
Insulin-Like Growth Factor I
Liver
Male
Pregnancy
RNA, Messenger
Rats
Rats, Sprague-Dawley