Faculty Collaboration Database

IUGR differentially alters MeCP2 expression and H3K9Me3 of the PPARγ gene in male and female rat lungs during alveolarization. Birth Defects Res A Clin Mol Teratol 2011 Aug;91(8):672-81

Date

03/23/2011

Pubmed ID

21425435

Pubmed Central ID

PMC3152656

DOI

10.1002/bdra.20783

Scopus ID

2-s2.0-79961162133 (requires institutional sign-in at Scopus site)   43 Citations

Abstract

Intrauterine growth restriction (IUGR) increases the risk of postnatal lung disease, with males more affected. In rat lungs, IUGR impairs alveolarization in conjunction with altered expression of peroxisome proliferator-activated receptor gamma (PPARγ). In non-lung cells, PPARγ transcription is regulated in part by the epigenetic modifying enzyme, and the methyl CpG binding protein 2 (MeCP2). However, it is unknown if IUGR affects MeCP2 expression or its interaction with PPARγ in the rat lung during alveolarization. In this study, we hypothesized that the rat lung would be characterized by the presence of MeCP2 short and long mRNA transcripts, MeCP2 protein isoforms, and the MeCP2 regulatory micro RNA, miR132. We further hypothesized that IUGR would, in a gender-specific manner, alter the levels of MeCP2 components in association with changes in PPARγ mRNA, MeCP2 occupancy at the PPARγ promoters, and PPARγ histone 3 lysine 9 trimethylation (H3K9Me3). To test these hypotheses, we used a well-characterized rat model of uteroplacental insufficiency-induced IUGR. We demonstrated the presence of MeCP2 mRNA, protein, and miR132 in the rat lung throughout alveolarization. We also demonstrated that IUGR alters MeCP2 expression and its interaction with PPARγ in a gender-divergent manner. We conclude that IUGR induces gender-specific alterations in the epigenetic milieu in the rat lung. We speculate that in the IUGR rat lung, this altered epigenetic milieu may predispose to gender-specific alterations in alveolarization.

Author List

Joss-Moore LA, Wang Y, Ogata EM, Sainz AJ, Yu X, Callaway CW, McKnight RA, Albertine KH, Lane RH

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

Animals
Animals, Newborn
Epigenesis, Genetic
Female
Fetal Growth Retardation
Gene Expression Regulation, Developmental
Histones
Male
Methyl-CpG-Binding Protein 2
MicroRNAs
PPAR gamma
Placental Insufficiency
Pregnancy
Pulmonary Alveoli
RNA, Messenger
Rats
Rats, Sprague-Dawley