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 inv...

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Bibliographic Details
Published in:Gene 2000-01, Vol.242 (1), p.407-418
Main Authors: Bigey, Pascal, Ramchandani, Shyam, Theberge, Johanne, Araujo, Felipe D., Szyf, Moshe
Format: Article
Language:English
Subjects:
Alternative Splicing
Animals
AP-1, activator protein 1
Base Sequence
Binding Sites
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA - chemistry
DNA - genetics
DNA - metabolism
DNA methylation
DNA methyltransferase
Dnmt1 gene
DNMT1, DNA methyltransferase 1
EMSA, electrophoretic mobility shift assay
Enhancers
Female
GC Rich Sequence
Gene Expression Regulation, Enzymologic
HeLa Cells
Hippocampus - enzymology
Humans
Molecular Sequence Data
Placenta - enzymology
Polymerase Chain Reaction
Promoter Regions, Genetic - genetics
Promoters
Protein Binding
Proto-Oncogene Proteins c-jun - physiology
RACE, rapid amplification cDNA ends
Ras signaling pathway
Regulatory Sequences, Nucleic Acid
Ribonucleases
Sequence Analysis, DNA
Transcription Factor AP-1 - metabolism
Transcription, Genetic
Tumor Cells, Cultured
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Summary: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.
ISSN:0378-1119
1879-0038
DOI:10.1016/S0378-1119(99)00501-6