title: Epigenetic analysis of the Dlk1-Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2-H19.
abstract: Dlk1 and Gtl2 are reciprocally imprinted genes located 80 kb apart on mouse chromosome 12. Similarities between this domain and that of the well characterized Igf2-H19 locus have been previously noted. Comparative genomic and epigenetic analysis of these two domains might help identify allele-specific epigenetic regulatory elements and common features involved in aspects of imprinting control. Here we describe a detailed methylation analysis of the Dlk1-Gtl2 domain on both parental alleles in the mouse. Like the Igf2-H19 domain, areas of differential methylation are hypermethylated on the paternal allele and hypomethylated on the maternal allele. Three differentially methylated regions (DMRs), each with different epigenetic characteristics, have been identified. One DMR is intergenic, contains tandem repeats and is the only region that inherits a paternal methylation mark from the germline. An intronic DMR contains a conserved putative CTCF-binding domain. All three DMRs have both unique and common features compared to those identified in the Igf2-H19 domain.
authors.affiliation: Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
authors.forename: Shuji
authors.initials: S
authors.lastname: Takada
authors.forename: Martina
authors.initials: M
authors.lastname: Paulsen
authors.forename: Maxine
authors.initials: M
authors.lastname: Tevendale
authors.forename: Chen-En
authors.initials: CE
authors.lastname: Tsai
authors.forename: Gavin
authors.initials: G
authors.lastname: Kelsey
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cattanach
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015152:Blotting, Northern; D000076246:CCCTC-Binding Factor; D002875:Chromosomes / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005809:Genes, Regulator; D005819:Genetic Markers / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D018398:Homeodomain Proteins; C420116:Ihit1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C422882:MEG3 non-coding RNA, mouse; D008565:Membrane Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D014157:Transcription Factors; C064045:delta protein; D007335:Insulin-Like Growth Factor II