PMID- 10325416 OWN - NLM STAT- MEDLINE DCOM- 19990804 LR - 20211203 IS - 0305-1048 (Print) IS - 0305-1048 (Linking) VI - 27 IP - 11 DP - 1999 Jun 1 TI - The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. PG - 2291-8 AB - 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. FAU - Robertson, K D AU - Robertson KD AD - University of Southern California, Norris Comprehensive Cancer Center, MS 83, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. FAU - Uzvolgyi, E AU - Uzvolgyi E FAU - Liang, G AU - Liang G FAU - Talmadge, C AU - Talmadge C FAU - Sumegi, J AU - Sumegi J FAU - Gonzales, F A AU - Gonzales FA FAU - Jones, P A AU - Jones PA LA - eng SI - GENBANK/AF129267 SI - GENBANK/AF129268 SI - GENBANK/AF129269 GR - R35 CA 49758/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 RN - 0 (DNA, Complementary) RN - 0 (DNMT3A protein, human) RN - 0 (Dnmt3a protein, mouse) RN - 0 (RNA, Messenger) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) RN - EC 2.1.1.37 (DNA Methyltransferase 3A) RN - EC 2.1.1.37 (DNA methyltransferase 3B) SB - IM MH - Alternative Splicing MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Chromosome Mapping MH - Chromosomes, Human, Pair 2 MH - Chromosomes, Human, Pair 20 MH - Colonic Neoplasms/*enzymology/genetics MH - DNA (Cytosine-5-)-Methyltransferases/*genetics MH - DNA Methyltransferase 3A MH - DNA, Complementary MH - Gene Expression MH - Humans MH - Kidney Neoplasms/*enzymology/genetics MH - Mice MH - Molecular Sequence Data MH - Pancreatic Neoplasms/*enzymology/genetics MH - RNA, Messenger MH - Sequence Homology, Amino Acid MH - Tissue Distribution MH - Urinary Bladder Neoplasms/*enzymology/genetics PMC - PMC148793 EDAT- 1999/05/15 00:00 MHDA- 1999/05/15 00:01 CRDT- 1999/05/15 00:00 PHST- 1999/05/15 00:00 [pubmed] PHST- 1999/05/15 00:01 [medline] PHST- 1999/05/15 00:00 [entrez] AID - gkc377 [pii] AID - 10.1093/nar/27.11.2291 [doi] PST - ppublish SO - Nucleic Acids Res. 1999 Jun 1;27(11):2291-8. doi: 10.1093/nar/27.11.2291.