Premium
Poor Postnatal Growth Is Correlated with Restricted Accessibility of STAT5B Response Element on IGF‐1 in a Gender‐specific Manner
Author(s) -
Fu Qi,
McKnight Robert A.,
Callaway Christopher W.,
Yu Xing,
Lane Robert H.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.698.6
Background Intrauterine growth restriction (IUGR) predisposes affected humans and rats towards poor postnatal growth. IUGR also decreases hepatic expression of IGF‐1, which regulates postnatal growth. Postnatal expression of hepatic IGF‐1 is controlled in large part through GH signaling via STAT5B binding. The rat IGF‐1 gene contains a STAT5B response element (RE) within intron 2. However, little is known about how IUGR affects this IGF‐1 STAT5B RE. We hypothesized that IUGR affects postnatal IGF‐1 DNA CpG methylation, histone code, and DNA accessibility of this STAT5B RE. Methods quantitative DNase I accessibility assay. Results Developmentally, CpG methylation decreases in d21 control relative to d0 control. IUGR deviated the normal epigenetic maturation changes in the following ways: 1) IUGR inhibited the normal demethylation process in males by increasing d21 CpG methylation 2) IUGR decreased d21 me3K4H3 and increased me3K9H3 accumulation in both genders. The preceding d21 changes significantly restricted accessibility of the IUGR hepatic intron 2 STAT5B RE in males, but not in females. Conclusion IUGR reduced DNA de‐methylation, altered the histone code, and limited DNA accessibility in the male hepatic IGF‐1 intron 2 STAT5B RE. We speculate that this represents an IUGR induced deviation from the normal maturational epigenetic processes that allow maximal GH induced STAT5B signaling.