Induction of DNA methylation and gene silencing by short interfering RNAs in human cells
- PMID: 15311210
- DOI: 10.1038/nature02889
Induction of DNA methylation and gene silencing by short interfering RNAs in human cells
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Induction of DNA methylation and gene silencing by short interfering RNAs in human cells.Nature. 2006 Jun 29;441(7097):1176. doi: 10.1038/nature04952. Nature. 2006. PMID: 16810259 No abstract available.
Abstract
Double-stranded RNAs (dsRNAs) induce post-transcriptional gene silencing in several species of animal and plant. In plants, dsRNAs targeted to CpG islands within a promoter can also induce RNA-directed DNA methylation; however, it remains unclear whether gene silencing mediated by DNA methylation can be induced by dsRNAs in mammalian cells. Here, we demonstrate that short interfering RNAs (siRNAs; 21-25-nucleotide RNA molecules) induce DNA methylation and histone H3 methylation in human cells. Synthetic siRNAs targeted to CpG islands of an E-cadherin promoter induced significant DNA methylation and histone H3 lysine 9 methylation in both MCF-7 and normal mammary epithelial cells. As a result, these siRNAs repressed expression of the E-cadherin gene at the transcriptional level. In addition, disrupting the expression of either one of two DNA methyltransferases (DNMT1 or DNMT3B) by specific siRNAs abolished the siRNA-mediated methylation of DNA. Moreover, vector-based siRNAs targeted to the erbB2 (also known as HER2) promoter also induced DNA methylation in MCF-7 cells. Thus, siRNAs targeted to CpG islands within the promoter of a specific gene can induce transcriptional gene silencing by means of DNA-methyltransferase-dependent methylation of DNA in human cells, and might have potential as a new type of gene therapeutic agent.
Comment in
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Further accusations rock Japanese RNA laboratory.Nature. 2006 Apr 6;440(7085):720-1. doi: 10.1038/440720a. Nature. 2006. PMID: 16598217 No abstract available.
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