Seila Amy C, Calabrese J Mauro, Levine Stuart S, Yeo Gene W, Rahl Peter B, Flynn Ryan A, Young Richard A, Sharp Phillip A
Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science. 2008 Dec 19;322(5909):1849-51. doi: 10.1126/science.1162253. Epub 2008 Dec 4.
Transcription initiation by RNA polymerase II (RNAPII) is thought to occur unidirectionally from most genes. Here, we present evidence of widespread divergent transcription at protein-encoding gene promoters. Transcription start site-associated RNAs (TSSa-RNAs) nonrandomly flank active promoters, with peaks of antisense and sense short RNAs at 250 nucleotides upstream and 50 nucleotides downstream of TSSs, respectively. Northern analysis shows that TSSa-RNAs are subsets of an RNA population 20 to 90 nucleotides in length. Promoter-associated RNAPII and H3K4-trimethylated histones, transcription initiation hallmarks, colocalize at sense and antisense TSSa-RNA positions; however, H3K79-dimethylated histones, characteristic of elongating RNAPII, are only present downstream of TSSs. These results suggest that divergent transcription over short distances is common for active promoters and may help promoter regions maintain a state poised for subsequent regulation.
人们认为，RNA聚合酶II（RNAPII）引发的转录从大多数基因开始是单向进行的。在此，我们展示了蛋白质编码基因启动子广泛存在双向转录的证据。转录起始位点相关RNA（TSSa-RNAs）非随机地位于活跃启动子两侧，在转录起始位点上游250个核苷酸处有反义短RNA峰，在转录起始位点下游50个核苷酸处有正义短RNA峰。Northern分析表明，TSSa-RNAs是长度为20至90个核苷酸的RNA群体的子集。与启动子相关的RNAPII和H3K4三甲基化组蛋白（转录起始的标志）在正义和反义TSSa-RNA位置共定位；然而，H3K79二甲基化组蛋白（延伸中的RNAPII的特征）仅存在于转录起始位点下游。这些结果表明，短距离的双向转录在活跃启动子中很常见，可能有助于启动子区域维持一个为后续调控做好准备的状态。
