RGD Reference Report - IUGR differentially alters MeCP2 expression and H3K9Me3 of the PPARgamma gene in male and female rat lungs during alveolarization. - Rat Genome Database

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IUGR differentially alters MeCP2 expression and H3K9Me3 of the PPARgamma gene in male and female rat lungs during alveolarization.

Authors: Joss-Moore, LA  Wang, Y  Ogata, EM  Sainz, AJ  Yu, X  Callaway, CW  McKnight, RA  Albertine, KH  Lane, RH 
Citation: Joss-Moore LA, etal., Birth Defects Res A Clin Mol Teratol. 2011 Aug;91(8):672-81. doi: 10.1002/bdra.20783. Epub 2011 Mar 21.
RGD ID: 8552971
Pubmed: PMID:21425435   (View Abstract at PubMed)
PMCID: PMC3152656   (View Article at PubMed Central)
DOI: DOI:10.1002/bdra.20783   (Journal Full-text)

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 (PPARgamma). In non-lung cells, PPARgamma 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 PPARgamma 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 PPARgamma mRNA, MeCP2 occupancy at the PPARgamma promoters, and PPARgamma 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 PPARgamma 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.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
PPARGHumanFetal Growth Retardation  ISOPparg (Rattus norvegicus)mRNA:decreased expression:lung (rat)RGD 
PpargRatFetal Growth Retardation  IEP mRNA:decreased expression:lung (rat)RGD 
PpargMouseFetal Growth Retardation  ISOPparg (Rattus norvegicus)mRNA:decreased expression:lung (rat)RGD 


Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Mecp2Ratlung alveolus development  IEP  RGD 

Molecular Function

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Mecp2Ratpromoter-specific chromatin binding  IDA  RGD 


Genes (Rattus norvegicus)
Mecp2  (methyl CpG binding protein 2) Pparg  (peroxisome proliferator-activated receptor gamma)

Genes (Mus musculus)
Pparg  (peroxisome proliferator activated receptor gamma)

Genes (Homo sapiens)
PPARG  (peroxisome proliferator activated receptor gamma)