Chromosome-Wide Analysis of Parental Allele-Specific Chromatin and DNA Methylation

Abstract

ABSTRACTTo reveal the extent of domain-wide epigenetic features at imprinted gene clusters, we performed a high-resolution allele-specific chromatin analysis of over 100 megabases along the maternally or paternally duplicated distal chromosome 7 (Chr7) and Chr15 in mouse embryo fibroblasts (MEFs). We found that reciprocal allele-specific features are limited to imprinted genes and their differentially methylated regions (DMRs), whereas broad local enrichment of H3K27me3 (BLOC) is a domain-wide feature at imprinted clusters. We uncovered novel allele-specific features of BLOCs. A maternally biased BLOC was found along theH19-Igf2domain. A paternal allele-specific gap was found alongKcnq1ot1, interrupting a biallelic BLOC in theKcnq1-Cdkn1cdomain. We report novel allele-specific chromatin marks at thePeg13andSlc38a4DMRs,Cdkn1cupstream region, andInpp5f_v2DMR and paternal allele-specific CTCF binding at thePeg13DMR. Additionally, we derived an imprinted gene predictor algorithm based on our allele-specific chromatin mapping data. The binary predictor H3K9ac and CTCF or H3K4me3 in one allele and H3K9me3 in the reciprocal allele, using a sliding-window approach, recognized with precision the parental allele specificity of known imprinted genes,H19,Igf2,Igf2as,Cdkn1c,Kcnq1ot1, andInpp5f_v2on Chr7 andPeg13andSlc38a4on Chr15. Chromatin features, therefore, can unequivocally identify genes with imprinted expression.