Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1999-8-4
pubmed:databankReference
pubmed:abstractText
DNA methylation in mammals is required for embryonic development, X chromosome inactivation and imprinting. Previous studies have shown that methylation patterns become abnormal in malignant cells and may contribute to tumorigenesis by improper de novo methylation and silencing of the promoters for growth-regulatory genes. RNA and protein levels of the DNA methyltransferase DNMT1 have been shown to be elevated in tumors, however murine stem cells lacking Dnmt1 are still able to de novo methylate viral DNA. The recent cloning of a new family of DNA methyltransferases (Dnmt3a and Dnmt3b) in mouse which methylate hemimethylated and unmethylated templates with equal efficiencies make them candidates for the long sought de novo methyltransferases. We have investigated the expression of human DNMT1, 3a and 3b and found widespread, coordinate expression of all three transcripts in most normal tissues. Chromosomal mapping placed DNMT3a on chromosome 2p23 and DNMT3b on chromosome 20q11.2. Significant overexpression of DNMT3b was seen in tumors while DNMT1 and DNMT3a were only modestly over-expressed and with lower frequency. Lastly, several novel alternatively spliced forms of DNMT3b, which may have altered enzymatic activity, were found to be expressed in a tissue-specific manner.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0305-1048
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2291-8
pubmed:dateRevised
2010-5-21
pubmed:meshHeading
pubmed-meshheading:10325416-Alternative Splicing, pubmed-meshheading:10325416-Amino Acid Sequence, pubmed-meshheading:10325416-Animals, pubmed-meshheading:10325416-Base Sequence, pubmed-meshheading:10325416-Chromosome Mapping, pubmed-meshheading:10325416-Chromosomes, Human, Pair 2, pubmed-meshheading:10325416-Chromosomes, Human, Pair 20, pubmed-meshheading:10325416-Colonic Neoplasms, pubmed-meshheading:10325416-DNA, Complementary, pubmed-meshheading:10325416-DNA (Cytosine-5-)-Methyltransferase, pubmed-meshheading:10325416-Gene Expression, pubmed-meshheading:10325416-Humans, pubmed-meshheading:10325416-Kidney Neoplasms, pubmed-meshheading:10325416-Mice, pubmed-meshheading:10325416-Molecular Sequence Data, pubmed-meshheading:10325416-Pancreatic Neoplasms, pubmed-meshheading:10325416-RNA, Messenger, pubmed-meshheading:10325416-Sequence Homology, Amino Acid, pubmed-meshheading:10325416-Tissue Distribution, pubmed-meshheading:10325416-Urinary Bladder Neoplasms
pubmed:year
1999
pubmed:articleTitle
The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors.
pubmed:affiliation
University of Southern California, Norris Comprehensive Cancer Center, MS 83, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't