Comparative Genome Analysis of the Mouse Imprinted Gene Impact and Its Nonimprinted Human Homolog IMPACT: Toward the Structural Basis for Species-Specific Imprinting
- Kohji Okamura1,6,
- Yuriko Hagiwara-Takeuchi1,6,
- Tao Li2,
- Thanh H. Vu2,
- Momoki Hirai3,
- Masahira Hattori4,
- Yoshiyuki Sakaki1,4,
- Andrew R. Hoffman2,7, and
- Takashi Ito1,5,7
- 1Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; 2VA Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California 94304, USA; 3Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo 113-0033, Japan; 4Human Genome Research Group, RIKEN Genomic Sciences Center, Wako, Saitama 351-0198, Japan; 5Division of Genome Biology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan
Abstract
Mouse Impact is a paternally expressed gene encoding an evolutionarily conserved protein of unknown function. Here we identified IMPACT, the human homolog of Impact, on chromosome 18q11.2–12.1, a region syntenic to the mouseImpact locus. IMPACT was expressed biallelically in brain and in various tissues from two informative fetuses and in peripheral blood from an informative adult. To reveal the structural basis for the difference in allelic expression between the two species, we elucidated complete genome sequences for both mouse Impact(∼38 kb) and human IMPACT (∼30 kb). Sequence comparison revealed that the two genes share a well-conserved exon–intron organization but bear significantly different CpG islands. The mouse island lies in the first intron and contains characteristic tandem repeats. Furthermore, this island serves as a differentially methylated region (DMR) consisting of a hypermethylated maternal allele and an unmethylated paternal allele. Intriguingly, this intronic island is missing from the nonimprinted human IMPACT, whose sole CpG island spans the first exon, lacks any apparent repeats, and escapes methylation on both chromosomes. These results suggest that the intronic DMR plays a role in the imprinting ofImpact.
[The sequence data described in this paper have been submitted to the DDBJ/EMBL/GenBank data library under accession nos. AB026264, AF232228, and AF232229.]
Footnotes
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↵6 These authors contributed equally to this work.
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↵7 Corresponding authors.
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E-MAIL arhoffman{at}leland.Stanford.EDU; FAX (650) 856-8024.
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E-MAIL titolab{at}kenroku.kanazawa-u.ac.jp; FAX 81 76 234 4508.
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Article and publication are at www.genome.org/cgi/doi/10.1101/gr.139200.
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- Received March 6, 2000.
- Accepted September 28, 2000.
- Cold Spring Harbor Laboratory Press
