[HTML][HTML] Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene

Q Fu, X Yu, CW Callaway, RH Lane… - The FASEB …, 2009 - ncbi.nlm.nih.gov
Q Fu, X Yu, CW Callaway, RH Lane, RA McKnight
The FASEB Journal, 2009ncbi.nlm.nih.gov
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 …
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.—Fu, Q., Yu, X., Callaway, CW, Lane, RH, McKnight, RA Epigenetics: intrauterine growth retardation (IUGR) modifies the histone code along the rat hepatic IGF-1 gene.
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