p53-Mediated Repression of DNA Methyltransferase 1 Expression by Specific DNA Binding
作者： Oliver Bögler , Erica J. Peterson , Shirley M. Taylor
DOI:
关键词: DNA methyltransferase 、 Regulation of gene expression 、 Epigenetics 、 Epigenetics of physical exercise 、 DNA methylation 、 Epigenomics 、 Molecular biology 、 Biology 、 DNMT1 、 Cancer epigenetics
摘要: Cytosine methylation patterns in genomic DNA are significantly altered cancer, and de novo CpG island has been implicated tumor suppressor gene silencing. Here we demonstrate a mechanistic link between the p53 control of epigenetic regulation by methylation. Deletion p53in HCT116 human colon carcinoma cells primary mouse astrocytes resulted 6-fold increase cytosine methyltransferase 1 (Dnmt1) mRNA protein, suggesting relief p53-mediated Dnmt1repression. A consensus binding site exon Dnmt1gene bound recombinant vitro endogenous vivo absence stimuli that activate p53, implying controls Dnmt1transcription through direct binding. Interestingly, ionizing radiation or etoposide, both which stabilize diminished chromatin immunoprecipitation assays, concomitant with 5-fold Dnmt1 levels. Our findings suggest activation reduces relieves transcriptional repression Dnmt1gene, whereas loss frequent, early event tumorigenesis, may contribute to aberrant
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