bidirectional transcription directs both transcriptional gene activation and suppression in human cells双向转录指导转录基因激活和抑制人体细胞.pdfVIP

Bidirectional Transcription Directs Both Transcriptional Gene Activation and Suppression in Human Cells 1 1 1,2 3 1,2 Kevin V. Morris *, Sharon Santoso , Anne-Marie Turner , Chiara Pastori , Peter G. Hawkins 1 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, United States of America, 2 The Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, California, United States of America, 3 Oncology Institute of Southern Switzerland, Bellinzona, Switzerland Abstract Small RNAs targeted to gene promoters in human cells have been shown to modulate both transcriptional gene suppression and activation. However, the mechanism involved in transcriptional activation has remained poorly defined, and an endogenous RNA trigger for transcriptional gene silencing has yet to be identified. Described here is an explanation for siRNA-directed transcriptional gene activation, as well as a role for non-coding antisense RNAs as effector molecules driving transcriptional gene silencing. Transcriptional activation of p21 gene expression was determined to be the result of Argonaute 2–dependent, post-transcriptional silencing of a p21-specific antisense transcript, which functions in Argonaute 1–mediated transcriptional control of p21 mRNA expression. The data presented here suggest that in human cells, bidirectional transcription is an endogenous gene regulatory mechanism whereby an antisense RNA directs epigenetic regulatory complexes to a sense promoter, resulting in RNA-directed epigenetic gene regulation. The observations presented