Premium
IUGR disrupts the PPARγ‐Setd8‐H4K20me1 loop in male rat adipose tissue (577.5)
Author(s) -
Riddle E,
Zou C.J.,
Trevenzoli I,
JossMoore L
Publication year - 2014
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.28.1_supplement.577.5
Subject(s) - adipose tissue , medicine , endocrinology , biology , peroxisome proliferator activated receptor , receptor
Intrauterine growth restriction (IUGR) programs adipose dysfunction. Appropriate adipose function is, in part, maintained by the peroxisome proliferator activated receptor gamma (PPARγ)‐Setd8‐H4K20me1 (histone 4, lysine 20, methylation) positive feedback loop. This loop relies on PPARγ’s direct transcriptional control of Setd8, as well as Setd8’s placement of H4K20me1 on PPARγ. We previously showed that IUGR causes adipose dysfunction and increases total PPARγ mRNA levels in male rat adipose tissue. However, the effect of IUGR on the PPARγ‐Setd8‐H4K20me1 loop in male rat adipose tissue is unknown. We hypothesize that IUGR disrupts the PPARγ‐Setd8‐H4K20me1 loop in male rat adipose tissue. IUGR was induced by bilateral uterine artery ligation in rat dams at E19 of gestation. Subcutaneous adipose tissue of male IUGR and control rats was assessed at postnatal day 21 (n=4 per group). PPARγ1, PPARγ2, and Setd8 mRNA levels were measured using real‐time PCR. Chromatin immunoprecipitation was used to quantify H4K20me1 at Promoter 1 (P1), P2 and the 3’UTR of the PPARγ gene. Results are IUGR as % of Control ± SEM, *p<0.05. IUGR increased PPARγ1 (227 ± 40*), PPARγ2 (195 ± 29*), and Setd8 (171 ± 28*) mRNA levels in male rat adipose tissue. IUGR decreased H4K20me1 at P1 of the PPARγ gene (44 ± 6*), with no significant changes at P2 or the 3’UTR. The PPARγ‐Setd8‐H4K20me1 loop plays an important role in adipose function and is disrupted by IUGR. Increased PPARγ and Setd8 mRNA in conjunction with decreased H4K20Me1 at PPARγ P1, suggests dysregulation of H4K20me1 placement or H4K20 demethylation. Our ongoing studies examine regulation of H4K20me1 placement on PPARγ as well as the function of the H4K20 demethylase, PHF8. Grant Funding Source : Supported by NIH grant DK084036(LJM)