共 40 条
Transcriptional regulation of the human DNA methyltransferase (dnmt1) gene
被引:104
作者:
Bigey, P
[1
]
Ramchandani, S
[1
]
Theberge, J
[1
]
Araujo, FD
[1
]
Szyf, M
[1
]
机构:
[1] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada
来源:
关键词:
DNA methylation;
DNA methyltransferase enhancers;
promoters;
Ras signaling pathway;
D O I:
10.1016/S0378-1119(99)00501-6
中图分类号:
Q3 [遗传学];
学科分类号:
071007 ;
090102 ;
摘要:
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 CC-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. (C) 2000 Elsevier Science B.V. All rights reserved.
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页码:407 / 418
页数:12
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