Chromosome-wide analysis of parental allele-specific chromatin and DNA methylation

Mol Cell Biol. 2011 Apr;31(8):1757-70. doi: 10.1128/MCB.00961-10. Epub 2011 Feb 14.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Alleles
  • Animals
  • Cells, Cultured
  • Chromatin / genetics*
  • Chromatin / metabolism*
  • Chromosomes*
  • DNA Methylation*
  • Histones / metabolism
  • Mice
  • Transcription, Genetic


  • Chromatin
  • Histones

Associated data

  • GEO/GSE26947