CpG methylation is maintained in human cancer cells lacking DNMT1

Hypermethylation is associated with the silencing of tumour susceptibility genes in several forms of cancer 1 , 2 ; however, the mechanisms responsible for this aberrant methylation are poorly understood 3 , 4 . The prototypic DNA methyltransferase, DNMT1, has been widely assumed to be responsible f...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) Vol. 404; no. 6781; pp. 1003 - 1007
Main Authors: Rhee, Ina, Jair, Kam-Wing, Yen, Ray-Whay Chiu, Lengauer, Christoph, Herman, James G., Kinzler, Kenneth W., Vogelstein, Bert, Baylin, Stephen B., Schuebel, Kornel E.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 27.04.2000
Nature Publishing
Nature Publishing Group
Subjects:
5-Methylcytosine
Biological and medical sciences
Blotting, Southern
Cancer
Colorectal carcinoma
Cytosine - analogs & derivatives
Cytosine - metabolism
Deoxyribonucleic acid
DNA
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases - deficiency
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA Methylation
DNMT1 gene
Gene Silencing
General aspects
Genes
Genes, p16
Humanities and Social Sciences
Humans
INK4a gene
letter
Medical sciences
Methylation
multidisciplinary
Pathology
Science
Science (multidisciplinary)
Tumor Cells, Cultured
Tumors
Rectal disease
Carcinoma
Reaction specificity
CpG island
Carcinogenesis
Genetic determinism
Gene
GC rich sequence
Established cell line
Intestinal disease
Colon
Tumor cell
Tumor suppressor gene
Human
Nucleotide sequence
Enzyme
Transferases
Malignant tumor
Colonic disease
Gene silencing
Methyltransferases
Rectum
Epigenetics
Digestive diseases
Hypermethylation
Genome
Methylation
ISSN:0028-0836, 1476-4687
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hypermethylation is associated with the silencing of tumour susceptibility genes in several forms of cancer 1 , 2 ; however, the mechanisms responsible for this aberrant methylation are poorly understood 3 , 4 . 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 5 , 6 . To test this hypothesis, we disrupted the DNMT1 gene through homologous recombination in human colorectal carcinoma cells. Here we show that cells lacking DNMT1 exhibited markedly decreased cellular DNA methyltransferase activity, but there was only a 20% decrease in overall genomic methylation. Although juxtacentromeric satellites became significantly demethylated, most of the loci that we analysed, including the tumour suppressor gene p16 INK4a , remained fully methylated and silenced. These results indicate that DNMT1 has an unsuspected degree of regional specificity in human cells and that methylating activities other than DNMT1 can maintain the methylation of most of the genome.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
ObjectType-Article-2
ObjectType-Feature-1
content type line 23
ISSN:0028-0836
1476-4687
DOI:10.1038/35010000