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Variable histone modifications at the A(vy) metastable epiallele

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Date
2010
Authors
Dolinoy, Dana C
Weinhouse, Caren
Jones, Tamara R
Rozek, Laura S
Jirtle, Randy L
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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.
Type
Other article
Subject
epigenetics
metastable epiallele
viable yellow agouti
histone
environmental epigenomics
epigenetic states
gene-expression
methylation
mouse
chromatin
cells
supplementation
transcription
acetylation
inheritance
biochemistry & molecular biology
Permalink
https://hdl.handle.net/10161/4198
Published Version (Please cite this version)
10.4161/epi.5.7.12892
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.
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