Promoter-specific transcriptional interference and c-myc gene silencing by siRNAs in human cells

摘要: Small interfering RNAs (siRNAs) directed to gene promoters can silence genes at the transcriptional level. siRNA-directed silencing (RdTS) was first described in plants and yeasts more recently mammalian cells. RdTS has been associated with induction of epigenetic changes formation complexes containing RNA interference chromatin-remodelling factors. Here, we show that a promoter-targeted siRNA inhibits transcription c-myc gene. Transcriptional did not involve known marks. Instead, interfered initiation blocking assembly pre-initiation complex. depended on Argonaute 2 noncoding promoter-associated initiated upstream overlapping start site. Silencing led growth arrest, reduced clonogenic potential senescence over-expressing prostate cancer cells minimal effect normal RNA-directed may be natural mechanism control siRNAs targeting participating this regulatory pathway could valuable tools expression deregulated human diseases.