Comparative genome analysis of the mouse imprinted gene IMPACT and its nonimprinted human homolog IMPACT:: Toward the structural basis for species-specific imprinting

被引:65
作者
Okamura, K
Hagiwara-Takeuchi, Y
Li, T
Vu, TH
Hirai, M
Hattori, M
Sakaki, Y
Hoffman, AR [1 ]
Ito, T
机构
[1] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Tokyo 1088639, Japan
[2] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA
[3] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA
[4] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Tokyo 1130033, Japan
[5] RIKEN, Gen Sci Ctr, Human Genome Res Grp, Wako, Saitama 3510198, Japan
[6] Kanazawa Univ, Canc Res Inst, Div Genome Biol, Kanazawa, Ishikawa 9200934, Japan
关键词
D O I
10.1101/gr.139200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mouse Impact 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 prays a role in the imprinting of Impact.
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收藏
页码:1878 / 1889
页数:12
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