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.
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.
Yatsuki
Hitomi
H
Department of Biochemistry, Saga Medical School, Saga, Saga 849-8501, Japan.
Joh
Keiichiro
K
Higashimoto
Ken
K
Soejima
Hidenobu
H
Arai
Yuji
Y
Wang
Youdong
Y
Hatada
Izuho
I
Obata
Yayoi
Y
Morisaki
Hiroko
H
Zhang
Zhongming
Z
Nakagawachi
Tetsuji
T
Satoh
Yuji
Y
Mukai
Tsunehiro
T
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
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