An evolutionary scenario for genomic imprinting of Impact lying between nonimprinted neighbors.
Mouse Impact is the sole imprinted gene mapped to chromosome 18 to date. Despite its remarkable evolutionary conservation, human IMPACT was shown to escape genomic imprinting. Here we identified Hrh4 and Osbpl1 as the distal and proximal nearest neighbors of Impact, respectively, and found that both genes are expressed biallelically. Thus, in contrast with most imprinted genes, Impact fails to show apparent physical clustering with other imprinted genes. Since Impact not only lies in an intergenic region but also consists of 11 exons, it does not seem to be an imprinted gene generated by a retrotransposition. Hazardous effects of overexpressed Impact, a genomic segment containing paralogues of Hrh4 and Osbpl1 but not of Impact, and enhanced promoter activity in the mouse led us to propose an alternative model. This model assumes that segmental duplication followed by enhancement of the promoter activity in the lineage to mouse is responsible for the species-specific imprinting of Impact.
Okamura
Kohji
K
Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Yamada
Yoichi
Y
Sakaki
Yoshiyuki
Y
Ito
Takashi
T
D000483:Alleles; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D019143:Evolution, Molecular; D005091:Exons; D018392:Genomic Imprinting; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D011968:Receptors, Histamine / Q000235:genetics; D000074040:Receptors, Histamine H4; D011987:Receptors, Steroid; D018626:Retroelements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013447:Sulfites / Q000494:pharmacology; D014018:Tissue Distribution; D000098825:Oxysterol Binding Proteins
D002352:Carrier Proteins; D018076:DNA, Complementary; C418607:HRH4 protein, human; C498829:Hrh4 protein, mouse; C498828:Hrh4 protein, rat; C484600:IMPACT protein, human; C107747:Impact protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D011987:Receptors, Steroid; D018626:Retroelements; D013447:Sulfites; D000098825:Oxysterol Binding Proteins