Large, male germ cell-specific hypomethylated DNA domains with unique genomic and epigenomic features on the mouse X chromosome

Rieko Ikeda, Hirosuke Shiura, Koji Numata, Michihiko Sugimoto, Masayo Kondo, Nathan Mise, Masako Suzuki, John M. Greally, Kuniya Abe

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

To understand the epigenetic regulation required for germ cell-specific gene expression in the mouse, we analysed DNA methylation profiles of developing germ cells using a microarray-based assay adapted for a small number of cells. The analysis revealed differentially methylated sites between cell types tested. Here, we focused on a group of genomic sequences hypomethylated specifically in germline cells as candidate regions involved in the epigenetic regulation of germline gene expression. These hypomethylated sequences tend to be clustered, forming large (10 kb to ∼9 Mb) genomic domains, particularly on the X chromosome of male germ cells. Most of these regions, designated here as large hypomethylated domains (LoDs), correspond to segmentally duplicated regions that contain gene families showing germ cell- or testis-specific expression, including cancer testis antigen genes. We found an inverse correlation between DNA methylation level and expression of genes in these domains. Most LoDs appear to be enriched with H3 lysine 9 dimethylation, usually regarded as a repressive histone modification, although some LoD genes can be expressed in male germ cells. It thus appears that such a unique epigenomic state associated with the LoDs may constitute a basis for the specific expression of genes contained in these genomic domains.

Original languageEnglish (US)
Pages (from-to)549-565
Number of pages17
JournalDNA Research
Volume20
Issue number6
DOIs
StatePublished - Dec 1 2013

Keywords

  • DNA methylation
  • cancer testis antigen
  • epigenome
  • primordial germ cell
  • reprogramming

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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