Transcriptional regulation of the human DNA Methyltransferase (dnmt1) gene.
DNA methylation is an important component of the epigenetic control of genome functions. Understanding the regulation of the DNA Methyltransferase (dnmt1) gene expression is critical for comprehending how DNA methylation is coordinated with other critical biological processes. In this paper, we investigate the transcriptional regulatory region of the human dnmt1 gene using a combination of RACE, RNase protection analysis and CAT assays. We identified one major and three minor transcription initiation sites in vivo (P1-P4), which are regulated by independent enhancers and promoter sequences. The minimal promoter elements of P1, P2 and P4 are mapped within 256 bp upstream of their respective transcription initiation sites. P1 is nested within a CG-rich area, similar to other housekeeping genes, whereas P2-P4 are found 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 the responsiveness of dnmt1 to oncogenic signals that are mediated by the Ras-c-Jun oncogenic signaling pathway.
Bigey
P
P
Department of Pharmacology and Therapeutics, McGill University, Montreal, PQ, Canada.
Ramchandani
S
S
Theberge
J
J
Araujo
F D
FD
Szyf
M
M
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D005260:Female; D020862:GC Rich Sequence; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid; D012260:Ribonucleases; D017422:Sequence Analysis, DNA; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D012260:Ribonucleases