Source:http://linkedlifedata.com/resource/pubmed/id/12410230
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2002-10-31
|
| pubmed:databankReference | |
| pubmed:abstractText |
Genomic imprinting is an epigenetic modification that results in expression from only one of the two parental copies of a gene. Differences in methylation between the two parental chromosomes are often observed at or near imprinted genes. Beckwith-Wiedemann syndrome (BWS), which predisposes to cancer and excessive growth, results from a disruption of imprinted gene expression in chromosome band 11p15.5. One third of individuals with BWS lose maternal-specific methylation at KvDMR1, a putative imprinting control region within intron 10 of the KCNQ1 gene, and it has been proposed that this epimutation results in aberrant imprinting and, consequently, BWS1, 2. Here we show that paternal inheritance of a deletion of KvDMR1 results in the de-repression in cis of six genes, including Cdkn1c, which encodes cyclin-dependent kinase inhibitor 1C. Furthermore, fetuses and adult mice that inherited the deletion from their fathers were 20-25% smaller than their wildtype littermates. By contrast, maternal inheritance of this deletion had no effect on imprinted gene expression or growth. Thus, the unmethylated paternal KvDMR1 allele regulates imprinted expression by silencing genes on the paternal chromosome. These findings support the hypothesis that loss of methylation in BWS patients activates the repressive function of KvDMR1 on the maternal chromosome, resulting in abnormal silencing of CDKN1C and the development of BWS.
|
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
|
| pubmed:issn |
1061-4036
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
32
|
| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
426-31
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12410230-Alleles,
pubmed-meshheading:12410230-Animals,
pubmed-meshheading:12410230-Beckwith-Wiedemann Syndrome,
pubmed-meshheading:12410230-Blotting, Northern,
pubmed-meshheading:12410230-Brain,
pubmed-meshheading:12410230-Chromosome Mapping,
pubmed-meshheading:12410230-Down-Regulation,
pubmed-meshheading:12410230-Fathers,
pubmed-meshheading:12410230-Female,
pubmed-meshheading:12410230-Gene Deletion,
pubmed-meshheading:12410230-Genomic Imprinting,
pubmed-meshheading:12410230-Male,
pubmed-meshheading:12410230-Mice,
pubmed-meshheading:12410230-Mice, Inbred C57BL,
pubmed-meshheading:12410230-Models, Genetic,
pubmed-meshheading:12410230-Molecular Sequence Data,
pubmed-meshheading:12410230-Mothers,
pubmed-meshheading:12410230-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:12410230-Physical Chromosome Mapping,
pubmed-meshheading:12410230-Up-Regulation
|
| pubmed:year |
2002
|
| pubmed:articleTitle |
Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1.
|
| pubmed:affiliation |
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|