DNMT1 and DNMT3b cooperate to silence genes in human cancer cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-04

AUTHORS

Ina Rhee, Kurtis E. Bachman, Ben Ho Park, Kam-Wing Jair, Ray-Whay Chiu Yen, Kornel E. Schuebel, Hengmi Cui, Andrew P. Feinberg, Christoph Lengauer, Kenneth W. Kinzler, Stephen B. Baylin, Bert Vogelstein

ABSTRACT

Inactivation of tumour suppressor genes is central to the development of all common forms of human cancer. This inactivation often results from epigenetic silencing associated with hypermethylation rather than intragenic mutations. In human cells, the mechanisms underlying locus-specific or global methylation patterns remain unclear. The prototypic DNA methyltransferase, Dnmt1, accounts for most methylation in mouse cells, but human cancer cells lacking DNMT1 retain significant genomic methylation and associated gene silencing. We disrupted the human DNMT3b gene in a colorectal cancer cell line. This deletion reduced global DNA methylation by less than 3%. Surprisingly, however, genetic disruption of both DNMT1 and DNMT3b nearly eliminated methyltransferase activity, and reduced genomic DNA methylation by greater than 95%. These marked changes resulted in demethylation of repeated sequences, loss of insulin-like growth factor II (IGF2) imprinting, abrogation of silencing of the tumour suppressor gene p16INK4a, and growth suppression. Here we demonstrate that two enzymes cooperatively maintain DNA methylation and gene silencing in human cancer cells, and provide compelling evidence that such methylation is essential for optimal neoplastic proliferation. More... »

PAGES

552-556

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/416552a

DOI

http://dx.doi.org/10.1038/416552a

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1014752081

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11932749


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/416552a'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/416552a'


 

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