title: Chromosome-wide analysis of parental allele-specific chromatin and DNA methylation.
abstract: To 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 the H19-Igf2 domain. A paternal allele-specific gap was found along Kcnq1ot1, interrupting a biallelic BLOC in the Kcnq1-Cdkn1c domain. We report novel allele-specific chromatin marks at the Peg13 and Slc38a4 DMRs, Cdkn1c upstream region, and Inpp5f_v2 DMR and paternal allele-specific CTCF binding at the Peg13 DMR. 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, and Inpp5f_v2 on Chr7 and Peg13 and Slc38a4 on Chr15. Chromatin features, therefore, can unequivocally identify genes with imprinted expression.
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, 1450 E. Duarte Road, Duarte, CA 91010, USA.
authors.forename: Purnima
authors.initials: P
authors.lastname: Singh
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Arthur X
authors.initials: AX
authors.lastname: Li
authors.forename: Tibor A
authors.initials: TA
authors.lastname: Rauch
authors.forename: Gerd P
authors.initials: GP
authors.lastname: Pfeifer
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Mann
authors.forename: Piroska E
authors.initials: PE
authors.lastname: Szabó
mesh_terms: D000465:Algorithms; D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D002875:Chromosomes; D019175:DNA Methylation; D006657:Histones / Q000378:metabolism; D051379:Mice; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones