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Allele-specific DNA methylation in mouse strains is mainly determined by cis-acting sequences.

ABSTRACT: DNA methylation is a vital epigenetic mark that participates in establishing and maintaining chromatin structures and regulates gene transcription during mammalian development and cellular differentiation. Differences in epigenetic patterns between individuals may contribute to phenotypic variation and disease susceptibility; however, little is known about the extent of such variation or how different epigenetic patterns are established. Here we have compared DNA methylation profiles of macrophages from two inbred mouse strains (C57BL/6 and BALB/c) at 181 large genomic intervals that were selected based on differential gene expression patterns. Using a DNA methylation-dependent fractionation approach based on a combination of methyl-CpG immunoprecipitation and locus-wide tiling arrays, we identified several hundred differentially methylated regions, and simultaneously uncovered previously unrecognized genetic variability between both mouse strains at the studied loci. DNA sequence and methylation differences were validated by DNA sequencing and mass spectrometry analysis of bisulfite-treated DNA for a subset of regions. Importantly, we show that in F1 hybrids, the majority of strain-specific methylation patterns in somatic cells were maintained on the parental allele, regardless of their status in the male germ line. The common association of differentially methylated regions with sequence polymorphisms suggests that the genomic context determines the developmentally regulated epigenetic status at most nonimprinted regions of mammalian genomes.

SUBMITTER: Schilling E

PROVIDER: S-EPMC2775599 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Allele-specific DNA methylation in mouse strains is mainly determined by cis-acting sequences.

Schilling Elmar E El Chartouni Carol C Rehli Michael M

Genome research 20090817 11

DNA methylation is a vital epigenetic mark that participates in establishing and maintaining chromatin structures and regulates gene transcription during mammalian development and cellular differentiation. Differences in epigenetic patterns between individuals may contribute to phenotypic variation and disease susceptibility; however, little is known about the extent of such variation or how different epigenetic patterns are established. Here we have compared DNA methylation profiles of macropha ...[more]

PMID: 19687144

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Project description:Gene expression divergence between closely related species could be attributed to both cis- and trans- DNA sequence changes during evolution, but it is unclear how the evolutionary dynamics of epigenetic marks are regulated. In eutherian mammals, biparental DNA methylation marks are erased and reset during gametogenesis, resulting in paternal or maternal imprints, which lead to genomic imprinting. Whether DNA methylation reprogramming exists in insects is not known. Wasps of the genus Nasonia are non-social parasitoids that are emerging as a model for studies of epigenetic processes in insects. In this study, we quantified allele-specific expression and methylation genome-wide in Nasonia vitripennis and Nasonia giraulti and their reciprocal F1 hybrids. No parent-of-origin effect in allelic expression was found for >8,000 covered genes, suggesting a lack of genomic imprinting in adult Nasonia. As we expected, both significant cis- and trans- effects are responsible for the expression divergence between N. vitripennis and N. giraulti. Surprisingly, all 178 differentially methylated genes are also differentially methylated between the two alleles in F1 hybrid offspring, recapitulating the parental methylation status with nearly 100% fidelity, indicating the presence of strong cis-elements driving the target of gene body methylation. In addition, we discovered that total and allele-specific expression are positively correlated with allele-specific methylation in a subset of the differentially methylated genes. The 100% cis-regulation in F1 hybrids suggests the methylation machinery is conserved and DNA methylation is targeted by cis features in Nasonia. The lack of genomic imprinting and parent-of-origin differentially methylated regions in Nasonia, together with the stable inheritance of methylation status between generations, suggests either a cis-regulatory motif for methylation at the DNA level or highly stable inheritance of an epigenetic signal in Nasonia.

Dataset Information

Allele-specific DNA methylation in mouse strains is mainly determined by cis-acting sequences.

Publications

Allele-specific DNA methylation in mouse strains is mainly determined by cis-acting sequences.

Similar Datasets

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