Transcriptional regulation of the human DNA methyltransferase (dnmt1) gene

DNA methylation is an important component of the epigenetic control of geno me Functions. Understanding the regulation of the DNA Methyltransferase (dn mt1) gene expression is critical for comprehending how DNA methylation is c oordinated with other critical biological processes. In this paper, we inve stigate the transcriptional regulatory region of the human dnmt1 gene using a combination of RACE, RNase protection analysis and CAT assays. We identi fied one major and three minor transcription initiation sites in vivo (P1-P 4), which are regulated by independent enhancers and promoter sequences. Th e minimal promoter elements of P1, P2 and P4 are mapped within 256 bp upstr eam of their respective transcription initiation sites. P1 is nested within a CC-rich area, similar to other housekeeping genes, whereas P2-P4 are fou nd in CG-poor areas. Three c-Jun-dependent enhancers are located downstream to P1 and upstream to P2-P4, thus providing a molecular explanation for th e responsiveness of dnmt1 to oncogenic signals that are mediated by the Ras -c-Jun oncogenic signaling pathway. (C) 2000 Elsevier Science B.V. All righ ts reserved.