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dc.contributor.author Jirtle, Randy en_US
dc.date.accessioned 2011-06-21T17:27:37Z
dc.date.available 2011-06-21T17:27:37Z
dc.date.issued 2010 en_US
dc.identifier.citation Dolinoy,Dana C.;Weinhouse,Caren;Jones,Tamara R.;Rozek,Laura S.;Jirtle,Randy L.. 2010. Variable histone modifications at the A(vy) metastable epiallele. Epigenetics 5(7): 637-644. en_US
dc.identifier.issn 1559-2294 en_US
dc.identifier.uri http://hdl.handle.net/10161/4198
dc.description.abstract The ability of environmental factors to shape health and disease involves epigenetic mechanisms that mediate gene-environment interactions. Metastable epiallele genes are variably expressed in genetically identical individuals due to epigenetic modifications established during early development. DNA methylation within metastable epialleles is stochastic due to probabilistic reprogramming of epigenetic marks during embryogenesis. Maternal nutrition and environment have been shown to affect metastable epiallele methylation patterns and subsequent adult phenotype. Little is known, however, about the role of histone modifications in influencing metastable epiallele expression and phenotypic variation. Utilizing chromatin immunoprecipitation followed by qPCR, we observe variable histone patterns in the 5' long terminal repeat (LTR) of the murine viable yellow agouti (A(vy)) metastable epiallele. This region contains 6 CpG sites, which are variably methylated in isogenic A(vy)/a offspring. Yellow mice, which are hypomethylated at the A(vy) LTR and exhibit constitutive ectopic expression of Agouti (a), also display enrichment of H3 and H4 di-acetylation (p = 0.08 and 0.09, respectively). Pseudoagouti mice, in which A(vy) hypermethylation is thought to silence ectopic expression, exhibit enrichment of H4K20 tri-methylation (p = 0.01). No differences are observed for H3K4 tri-methylation (p = 0.7), a modification often enriched in the promoter of active genes. These results show for the first time the presence of variable histone modifications at a metastable epiallele, indicating that DNA methylation acts in concert with histone modifications to affect inter-individual variation of metastable epiallele expression. Therefore, the potential for environmental factors to influence histone modifications, in addition to DNA methylation, should be addressed in environmental epigenomic studies. en_US
dc.language.iso en_US en_US
dc.publisher LANDES BIOSCIENCE en_US
dc.relation.isversionof doi:10.4161/epi.5.7.12892 en_US
dc.subject epigenetics en_US
dc.subject metastable epiallele en_US
dc.subject viable yellow agouti en_US
dc.subject histone en_US
dc.subject environmental epigenomics en_US
dc.subject epigenetic states en_US
dc.subject gene-expression en_US
dc.subject methylation en_US
dc.subject mouse en_US
dc.subject chromatin en_US
dc.subject cells en_US
dc.subject supplementation en_US
dc.subject transcription en_US
dc.subject acetylation en_US
dc.subject inheritance en_US
dc.subject biochemistry & molecular biology en_US
dc.title Variable histone modifications at the A(vy) metastable epiallele en_US
dc.title.alternative en_US
dc.description.version Version of Record en_US
duke.date.pubdate 2010-10-1 en_US
duke.description.endpage 644 en_US
duke.description.issue 7 en_US
duke.description.startpage 637 en_US
duke.description.volume 5 en_US
dc.relation.journal Epigenetics en_US

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