Cloning, expression and chromosome locations of the human DNMT3 gene family

DNA methylation plays an important role in animal development and gene regu lation. In mammals, several genes encoding DNA cytosine methyltransferases have been identified. DNMT1 is constitutively expressed and is required for the maintenance of global methylation after DNA replication. In contrast, the murine Dnmt3 family genes appear to be developmentally regulated and be have like de novo DNA methyltransferases in vitro. In this study, we have c loned human DNMT3A and DNMT3B that encode full-length DNMT3A and DNMT3B pro teins with 98% and 94% amino acid sequence identity to their murine homolog ues. The DNMT3A and DNMT3B show high homology in the carboxy terminal catal ytic domain and contain a conserved cysteine-rich region, which shares homo logy with the X-linked ATRX gene of the SNF2/SWI family. We have mapped hum an DNMT3A and DNMT3B to chromosomes 2p23 and 20q11.2 respectively, and dete rmined the DNMT3B genomic structure. We further show that DNMT3A expression is ubiquitous and can be readily detected in most adult tissues, whereas D NMT3B is expressed at very low levels in most tissues except testis, thyroi d and bone marrow. Significantly, both DNMT3A and DNMT3B expression is elev ated in several tumor cell lines to levels comparable to DNMT1. The cloning of the human DNMT3 genes will facilitate further biochemical and genetic s tudies of their functions in establishment of DNA methylation patterns, reg ulation of gene expression and tumorigenesis. (C) 1999 Elsevier Science B.V . All rights reserved.