An Essential Role for DNA Methyltransferase DNMT3B in Cancer Cell Survival*

@article{Beaulieu2002AnER,
  title={An Essential Role for DNA Methyltransferase DNMT3B in Cancer Cell Survival*},
  author={Normand Beaulieu and Steves Morin and Ian C Chute and M. F. Robert and Hannah Nguyen and A. Robert Macleod},
  journal={The Journal of Biological Chemistry},
  year={2002},
  volume={277},
  pages={28176 - 28181}
}
Abnormal methylation and associated silencing of tumor suppressor genes is a common feature of many types of cancers. The observation of persistent methylation in human cancer cells lacking the maintenance methyltransferase DNMT1 suggests the involvement of other DNA methyltransferases in gene silencing in cancer. To test this hypothesis, we have evaluated methylation and gene expression in cancer cells specifically depleted of DNMT3A or DNMT3B,de novo methyltransferases that are expressed in… 
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References

SHOWING 1-10 OF 32 REFERENCES
DNMT1 and DNMT3b cooperate to silence genes in human cancer cells
TLDR
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.
CpG methylation is maintained in human cancer cells lacking DNMT1
TLDR
It is shown that cells lacking DNMT1 exhibited markedly decreased cellular DNA methyltransferase activity, but there was only a 20% decrease in overall genomic methylation, indicating thatDNMT1 has an unsuspected degree of regional specificity in human cells and that methylating activities other than DN MT1 can maintain the methylation of most of the genome.
The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors.
TLDR
Investigation of the expression of human DNMT1, 3a and 3b found widespread, coordinate expression of all three transcripts in most normal tissues, and several novel alternatively spliced forms of DNMT3b, which may have altered enzymatic activity, were found to be expressed in a tissue-specific manner.
DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development
Differential mRNA expression of the human DNA methyltransferases (DNMTs) 1, 3a and 3b during the G(0)/G(1) to S phase transition in normal and tumor cells.
TLDR
Analysis of the expression of the mRNAs for DNMT1, 3a and 3b during the cell cycle of normal and transformed cells revealed a new level of control exerted over the cellular DNA methylation machinery, the loss of which provides an alternative mechanism for the genesis of the aberrant methylation patterns observed in tumor cells.
Dnmt3a and Dnmt3b Are Transcriptional Repressors That Exhibit Unique Localization Properties to Heterochromatin*
TLDR
It is demonstrated that the recently identified DNA methyltransferases, DnMT3a and Dnmt3b, like DNMT1, repress transcription in a methylation-independent manner and are important to the fact that mutations in DNMT3B are found in the developmental syndrome, ICF (immunodeficiency, centromeric heterochromatin instability, and facial anomalies).
Cloning, expression and chromosome locations of the human DNMT3 gene family.
DNA methyltransferase expression and DNA methylation of CPG islands and peri‐centromeric satellite regions in human colorectal and stomach cancers
TLDR
Both over‐expression of the maintenance DNA methyltransferase DNMT1 and over-expression of a newly identified de novo DNA methyl transferase, DNMT3b, are involved in human carcinogenesis, probably at different stages and through different mechanisms.
The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome.
TLDR
The first example of naturally occurring mutations in a mammalian DNA methyltransferase gene is described, occurring in patients with a rare autosomal recessive disorder, termed the ICF syndrome, for immunodeficiency, centromeric instability, and facial anomalies.
Down-regulation of Human DNA-(Cytosine-5) Methyltransferase Induces Cell Cycle Regulators p16 ink4A and p21WAF/Cip1 by Distinct Mechanisms*
TLDR
The results suggest that the elevated levels of DNA MeTase seen in cancer cells can inhibit tumor suppressors by distinct mechanisms involving either transcriptional inactivation through DNA methylation or by a methylation independent regulation.
...
...