Variable histone modifications at the A(vy) metastable epiallele
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 articleSubject
epigeneticsmetastable epiallele
viable yellow agouti
histone
environmental epigenomics
epigenetic states
gene-expression
methylation
mouse
chromatin
cells
supplementation
transcription
acetylation
inheritance
biochemistry & molecular biology
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https://hdl.handle.net/10161/4198Published Version (Please cite this version)
10.4161/epi.5.7.12892Citation
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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