title: Large, male germ cell-specific hypomethylated DNA domains with unique genomic and epigenomic features on the mouse X chromosome.
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.
authors.affiliation: 1Technology and Development Team for Mammalian Genome Dynamics, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba City, Ibaraki 305-0074, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Ikeda
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Shiura
authors.forename: Koji
authors.initials: K
authors.lastname: Numata
authors.forename: Michihiko
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Masayo
authors.initials: M
authors.lastname: Kondo
authors.forename: Nathan
authors.initials: N
authors.lastname: Mise
authors.forename: Masako
authors.initials: M
authors.lastname: Suzuki
authors.forename: John M
authors.initials: JM
authors.lastname: Greally
authors.forename: Kuniya
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002460:Cell Line; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D020440:Gene Duplication; D020869:Gene Expression Profiling; D005854:Germ Cells / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D056916:Segmental Duplications, Genomic; D013737:Testis / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; C489518:Mageb1 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C085792:Slx protein, mouse
keywords: DNA methylation; cancer testis antigen; epigenome; primordial germ cell; reprogramming