title: Domain regulation of imprinting cluster in Kip2/Lit1 subdomain on mouse chromosome 7F4/F5: large-scale DNA methylation analysis reveals that DMR-Lit1 is a putative imprinting control region.
abstract: Mouse chromosome 7F4/F5, where the imprinting domain is located, is syntenic to human 11p15.5, the locus for Beckwith-Wiedemann syndrome. The domain is thought to consist of the two subdomains Kip2 (p57(kip2))/Lit1 and Igf2/H19. Because DNA methylation is believed to be a key factor in genomic imprinting, we performed large-scale DNA methylation analysis to identify the cis-element crucial for the regulation of the Kip2/Lit1 subdomain. Ten CpG islands (CGIs) were found, and these were located at the promoter sites, upstream of genes, and within intergenic regions. Bisulphite sequencing revealed that CGIs 4, 5, 8, and 10 were differentially methylated regions (DMRs). CGIs 4, 5, and 10 were methylated paternally in somatic tissues but not in germ cells. CGI8 was methylated in oocyte and maternally in somatic tissues during development. Parental-specific DNase I hypersensitive sites (HSSs) were found near CGI8. These data indicate that CGI8, called DMR-Lit1, is not only the region for gametic methylation but might also be the imprinting control region (ICR) of the subdomain.
authors.affiliation: Department of Biochemistry, Saga Medical School, Saga, Saga 849-8501, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yatsuki
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Joh
authors.forename: Ken
authors.initials: K
authors.lastname: Higashimoto
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Arai
authors.forename: Youdong
authors.initials: Y
authors.lastname: Wang
authors.forename: Izuho
authors.initials: I
authors.lastname: Hatada
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Obata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Morisaki
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Nakagawachi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Satoh
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Mukai
mesh_terms: D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D050761:Cyclin-Dependent Kinase Inhibitor p57; D019175:DNA Methylation; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D016147:Genes, Tumor Suppressor; D018392:Genomic Imprinting / Q000235:genetics*; D005854:Germ Cells / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D019901:Locus Control Region / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D020161:Physical Chromosome Mapping; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000096:biosynthesis / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: C493964:CDKN1C protein, human; C493965:Cdkn1c protein, mouse; D002843:Chromatin; D050761:Cyclin-Dependent Kinase Inhibitor p57; C449939:KCNQ1OT1 RNA; D009687:Nuclear Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C118513:TSSC4 protein, human; D025521:Tumor Suppressor Proteins