Inactive or moderately active human promoters are enriched for inter-individual epialleles

Genome Biology
Carolina GemmaVardhman K Rakyan

Abstract

Inter-individual epigenetic variation, due to genetic, environmental or random influences, is observed in many eukaryotic species. In mammals, however, the molecular nature of epiallelic variation has been poorly defined, partly due to the restricted focus on DNA methylation. Here we report the first genome-scale investigation of mammalian epialleles that integrates genomic, methylomic, transcriptomic and histone state information. First, in a small sample set, we demonstrate that non-genetically determined inter-individual differentially methylated regions (iiDMRs) can be temporally stable over at least 2 years. Then, we show that iiDMRs are associated with changes in chromatin state as measured by inter-individual differences in histone variant H2A.Z levels. However, the correlation of promoter iiDMRs with gene expression is negligible and not improved by integrating H2A.Z information. We find that most promoter epialleles, whether genetically or non-genetically determined, are associated with low levels of transcriptional activity, depleted for housekeeping genes, and either depleted for H3K4me3/enriched for H3K27me3 or lacking both these marks in human embryonic stem cells. The preferential enrichment of iiDMRs at regions o...Continue Reading

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Aug 7, 2013·Human Molecular Genetics·Andrew E TeschendorffStephan Beck
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Related Concepts

Alleles
Histone H7
Early Promoters, Genetic
Monozygotic Twins
Genome, Human
DNA Methylation
Genomics
Epigenesis, Genetic
Embryonic Stem Cells
Antigens, Differentiation

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