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Author  |
Esteve, P.-O.; Chin, H.G.; Pradhan, S. |
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Title |
Human maintenance DNA (cytosine-5)-methyltransferase and p53 modulate expression of p53-repressed promoters |
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Journal Article |
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Year |
2005 |
Publication |
Proceedings of the National Academy of Sciences of the United States of America |
Abbreviated Journal |
Proc Natl Acad Sci U S A |
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Volume |
102 |
Issue |
4 |
Pages |
1000-1005 |
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Keywords |
Cell Line; DNA (Cytosine-5-)-Methyltransferase/physiology; DNA Methylation; Gene Expression Regulation; Gene Silencing; Humans; Microtubule-Associated Proteins/genetics; Neoplasm Proteins; Promoter Regions, Genetic; Tumor Suppressor Protein p53/physiology |
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Abstract |
DNA (cytosine-5)-methyltransferase (DNMT) 1 participates in transcriptional repression of genes by methylation-dependent and -independent mechanisms. Here, DNMT1 is shown to bind p53 and colocalize in the nucleus. DNMT1-mediated methylation is stimulated by p53 in vitro. Upon p53 induction, a reporter construct containing the antiapoptotic gene survivin promoter, which contains a natural p53 binding site, was methylated in WT HCT116 cells but not in DNMT1 null or p53 null cells. Endogenous survivin gene repression involves cooperation between DNMT1 and p53 and is relieved by introduction of DNMT1- or p53-specific small inhibitory RNA. DNMT1 null cells did not exhibit a significant repressive effect for p53 responsive survivin and cdc25C gene expression compared with the parental cells. Normal human fibroblasts also exhibited similar DNMT1- and p53-mediated methylation of the survivin promoter, suggesting cooperation between p53 and DNMT1 in gene silencing. |
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Address |
New England Biolabs, 32 Tozer Road, Beverly, MA 01915, USA |
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Language |
English |
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ISSN |
0027-8424 |
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Notes |
PMID:15657147 |
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no |
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Call Number |
pubs @ support @ |
Serial |
9257 |
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