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Fetal Origins of Lung Disease: PPARγ and Epigenetics
Author(s) -
JossMoore Lisa
Publication year - 2010
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.24.1_supplement.401.2
Subject(s) - epigenetics , biology , histone , dna methylation , peroxisome proliferator activated receptor , regulation of gene expression , bronchopulmonary dysplasia , gene expression , methylation , transcriptional regulation , gene , genetics , pregnancy , gestational age
Fetal and early life events impact the developing lung, contributing to an increased risk of bronchopulmonay dysplasia and potentially increasing the incidence of adult pulmonary disorders. The transcriptional regulator PPARγ is important for lung development and its effects are likely the result of epigenetic mechanisms. Epigenetic determinants include DNA methylation and covalent modifications of histones. PPARγ gene products arise from the use of multiple promoters and alternative splicing; as such, PPARγ relies on epigenetics to affect appropriate gene expression. In addition, recent studies have demonstrated that PPARγ targets the histone lysine methyltransferase, Setd8, an enzyme that places a methyl group on lysine (K)20 of histone(H) 4. Importantly, Setd8 places this mark on histones associated with the PPARγ gene in addition to other targets. Animal studies have demonstrated reduced PPARγ mRNA and protein levels in the lung in response to numerous perinatal insults. In fetal growth restricted rat lungs, PPARγ levels are reduced in conjunction with reduced Setd8 levels. The H4K20Me mark is also decreased on the PPARγ gene and other genes important in lung developmental outcome. We speculate that one way that PPARγ effects lung development is by regulating levels of Setd8 and the H4K20Me mark on PPARγ as well as other target genes.