Human maintenance DNA (cytosine-5)-methyltransferase and p53 modulate expression of p53-repressed promoters

• Pierre-Olivier Estève

  New England Biolabs, 32 Tozer Road, Beverly, MA 01915

• Hang Gyeong Chin

  New England Biolabs, 32 Tozer Road, Beverly, MA 01915

• Sriharsa Pradhan

  New England Biolabs, 32 Tozer Road, Beverly, MA 01915

抄録

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.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 102 (4), 1000-1005, 2005-01-18

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1363388845908249856
• NII論文ID: 30016244964
• DOI: 10.1073/pnas.0407729102
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.0407729102
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