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Show 137 school of medicine and health sciences UNDERGRADUATE RESEARCH ABSTRACTS Intrauterine growth restriction (IUGR) increases the risk of postnatal lung disease and impairs lung devel-opment. Lung development depends on programming of elastin expression during a critical developmen-tal window. In the rat, this critical window begins at birth. The programming of the elastin gene expression may be influenced by epigenetics. Epigenetic modifications include methylation of both DNA and histone proteins. Methylation of histone 4, lysine 20 (H4K20Me) along the elastin gene is dependent upon PPAR. Normal PPAR function depends on levels of DHA, a fatty acid that is reduced in IUGR. We showed that IUGR decreases rat lung elastin and PPAR expression at birth. We hypothesize that IUGR alters H4K20Me, as well as DNA methylation, along the elastin gene in newborn rat lung. IUGR was induced by bilateral uterine artery ligation in rat dams at E19 of gestation (term 21 days). Bisul-fite sequencing was used to assess DNA methylation within Exon 1 of the elastin gene in newborn IUGR and control rat lung. ChIP was used to assess H4K20Me levels along the elastin gene in the same samples. Results are reported as IUGR as % of gender-matched control ±SE. IUGR increased DNA methylation within exon 1 of the elastin gene in male newborn rat lung (160±21%*), with no significant change in female rat lungs. IUGR increased H4K20Me in the promoter region of the elastin gene in male (160±20%*) and fe-male (128±12%*) newborn rat lungs. IUGR also increased H4K20Me within the 3'UTR of elastin (189±8%*) in male rat lungs, with no change in females. *p 0.05 We conclude that IUGR alters the epigenetic programming of the elastin gene in male and female new-born rat lung. Given that elastin expression in the IUGR rat lung is decreased similarly in male and female lungs, gender-specific alterations in epigenetics are intriguing. We speculate that normalizing elastin H4K20Me in IUGR rat lung, for example by antenatal administration of DHA, may improve elastin expres-sion and lung phenotype in IUGR rats. IUGR ALTERS DNA AND HISTONE METHYLATION OF THE ELASTIN GENE IN NEWBORN RAT LUNG Anthony Sainz (Lisa A. Joss-Moore) Department of Pediatrics/Neonatology University of Utah Anthony Sainz Lisa A. Joss-Moore |