CpG methylation is maintained in human cancer cells lacking DNMT1

  title={CpG methylation is maintained in human cancer cells lacking DNMT1},
  author={Ina Rhee and Kam-wing Jair and Ray-Whay Chiu Yen and Christoph Lengauer and James Gordon Herman and Kenneth W. Kinzler and Bert Vogelstein and Stephen B. Baylin and Kornel E. Schuebel},
Hypermethylation is associated with the silencing of tumour susceptibility genes in several forms of cancer; however, the mechanisms responsible for this aberrant methylation are poorly understood. The prototypic DNA methyltransferase, DNMT1, has been widely assumed to be responsible for most of the methylation of the human genome, including the abnormal methylation found in cancers. To test this hypothesis, we disrupted the DNMT1 gene through homologous recombination in human colorectal… 
DNMT1 and DNMT3b cooperate to silence genes in human cancer cells
It is demonstrated that two enzymes cooperatively maintain DNA methylation and gene silencing in human cancer cells, and compelling evidence that such methylation is essential for optimal neoplastic proliferation is provided.
DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells
Results indicate that DNMT1 is necessary and sufficient to maintain global methylation and aberrant CpG island methylation in human cancer cells.
An Essential Role for DNA Methyltransferase DNMT3B in Cancer Cell Survival*
Results indicate that DNMT3B has significant site selectivity that is distinct from DNMT1, regulates aberrant gene silencing, and is essential for cancer cell survival.
Aberrant DNA methylation as a cancer-inducing mechanism.
  • M. Esteller
  • Biology
    Annual review of pharmacology and toxicology
  • 2005
The introduction of bisulfite-PCR methodologies combined with new genomic approaches provides a comprehensive spectrum of the genes undergoing this epigenetic change across all malignancies, and the use of some hypermethylated genes as biomarkers of the disease should be validated.
Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases.
The results demonstrate the role of DNMT1 and DNMT3b in CpG island methylation associated silencing and the usefulness of genetic disruption strategies in searching for new hypermethylated loci.
De novo CpG island methylation in human cancer cells.
A new assay for de novo activity of DNMTs is provided and data is suggested suggesting a potential role for DNMT1 in the initiation of promoter CpG island hypermethylation in human cancer cells.
The role of epigenetic transcription repression and DNA methyltransferases in cancer
The main epigenetic mechanisms for regulating transcription and its implications in cancer development are reviewed, including methylation‐mediated gene inactivation, which is associated with chromosomal instability and transcription repression.
Deep proteomic analysis of Dnmt1 mutant/hypomorphic colorectal cancer cells reveals dys-regulation of Epithelial-Mesenchymal Transition and subcellular re-localization of Beta-Catenin
The first comprehensive proteomic analysis of the widely studied Dnmt1 hypomorph colorectal cancer cells is presented and redistribution of DnMT1 and its interaction partner Beta-Catenin is identified as well as the dysregulation of EMT related processes and signalling pathways related to the development of a cancer stem cell phenotype.
CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future
Basic and translational studies will both be needed in the near future to fully understand the mechanisms, roles and uses of CpG island hypermethylation in human cancer.
Discovery of epigenetically silenced genes by methylated DNA immunoprecipitation in colon cancer cells.
The results show the usefulness of DNMT genetic disruption strategies combined with methylated DNA immunoprecipitation in searching for unknown hypermethylated candidate genes in human cancer that might aid the understanding of the biology of the disease and be of potential translational use.


CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression.
The results suggest that deregulation of DNA methyltransferase gene expression does not play a role in establishing tumor-specific abnormal DNA methylation patterns in human colorectal cancer.
Reduced genomic 5-methylcytosine content in human colonic neoplasia.
Surprisingly, three patients with the highest 5-methylcytosine content in their normal colon appear to have a germline predisposition to cancer (Lynch syndrome), suggesting a pervasive abnormality in the control of DNA methylation.
DNA methylation and genetic instability in colorectal cancer cells.
A striking difference in the expression of exogenously introduced retroviral genes in various colorectal cancer cell lines was reported and was associated with DNA methylation and could be reversed by treatment with the demethylating agent 5-azacytidine.
Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer
Although DNA methylation and histone deacetylation appear to act as synergistic layers for the silencing of genes in cancer, dense CpG island methylation is dominant for the stable maintenance of a silent state at these loci.
Mechanisms for the involvement of DNA methylation in colon carcinogenesis.
Biochemical conditions favoring a mutagenic pathway of C --> U --> T were not found in a target tissue known to undergo a high rate of C ― T transitions at CpG sites, suggesting an alternative mechanism to create these mutations.
De novo methylation of CpG island sequences in human fibroblasts overexpressing DNA (cytosine-5-)-methyltransferase
The data indicate that overexpression of DNA MTase can drive the de novo methylation of susceptible CpG island loci, thus providing support for the idea that DNAMTase can contribute to tumor progression through C pG island methylation-mediated gene inactivation.
Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.
The use of MSP is demonstrated to identify promoter region hypermethylation changes associated with transcriptional inactivation in four important tumor suppressor genes (p16, p15, E-cadherin and von Hippel-Lindau) in human cancer.