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

  1. Hitomi Yatsuki1,
  2. Keiichiro Joh1,
  3. Ken Higashimoto1,
  4. Hidenobu Soejima1,
  5. Yuji Arai2,
  6. Youdong Wang1,
  7. Izuho Hatada3,
  8. Yayoi Obata3,
  9. Hiroko Morisaki2,
  10. Zhongming Zhang1,
  11. Tetsuji Nakagawachi1,
  12. Yuji Satoh1, and
  13. Tsunehiro Mukai1,4
  1. 1Department of Biochemistry, Saga Medical School, Saga, Saga 849-8501, Japan; 2Department of Bioscience, National Cardiovascular Center Research Institute, Fujishiro-dai, Suita, Osaka 565-8565, Japan; 3Gene Research Center, Gunma University, Showa-machi, Maebashi 371-8511, Japan

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 (p57kip2)/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 thecis-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.

Footnotes

  • ↵4 Corresponding author.

  • E-MAIL mukait{at}post.saga-med.ac.jp; FAX 81-952-34-2067.

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.110702.

    • Received January 19, 2002.
    • Accepted September 10, 2002.
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  1. doi: 10.1101/gr.110702 Genome Res. 12: 1860-1870 Cold Spring Harbor Laboratory Press

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