title: IUGR differentially alters MeCP2 expression and H3K9Me3 of the PPARγ gene in male and female rat lungs during alveolarization.
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.
authors.affiliation: Division of Neonatology, University of Utah, 295 Chipeta Way 2N141, Salt Lake City, UT 84108, USA. Lisa.Joss-Moore@hsc.utah.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Joss-Moore
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Ogata
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Sainz
authors.forename: Xing
authors.initials: X
authors.lastname: Yu
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Callaway
authors.forename: Robert A
authors.initials: RA
authors.lastname: McKnight
authors.forename: Kurt H
authors.initials: KH
authors.lastname: Albertine
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lane
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010927:Placental Insufficiency / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000196:embryology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006657:Histones; C548821:MIRN132 microRNA, rat; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; D047495:PPAR gamma; D012333:RNA, Messenger