Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse.
p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP is located on chromosome 11p15.5 (ref. 2), a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a familial cancer syndrome, marking it a tumour suppressor candidate. Several types of childhood tumours including Wilm's tumour, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the Beckwith-Wiedemann syndrome has indicated maternal carriers as well as suggested a role in genomic imprinting. Here, as a first step towards elucidating the genesis of human cancers in this region, we showed that a mouse homologue of p57KIP2 is genomically imprinted. The paternally inherited allele is transcriptionally repressed and methylated. This murine gene maps to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin-2, insulin-like growth factor-2, H19 and Mash2 (refs 14-18).
Hatada
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I
National Cardiovascular Center Research Institute, Osaka, Japan.
Mukai
T
T
D000306:Adrenal Cortex Neoplasms / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003433:Crosses, Genetic; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D017931:DNA Primers; D004791:Enzyme Inhibitors; D005260:Female; D016147:Genes, Tumor Suppressor; D006580:Genetic Carrier Screening; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009115:Muridae; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012208:Rhabdomyosarcoma / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics
C493964:CDKN1C protein, human; C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D017931:DNA Primers; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D018844:Cyclin-Dependent Kinases