Kanduri Chandrasekhar, Thakur Noopur, Pandey Radha Raman
Department of Development and Genetics, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
EMBO J. 2006 May 17;25(10):2096-106. doi: 10.1038/sj.emboj.7601090. Epub 2006 Apr 20.
The underlying mechanisms linking antisense RNA, chromatin architecture and gene expression have not been fully elucidated. Here we show that long transcripts encoded from the Kcnq1ot1 antisense promoter silence the flanking genes more efficiently than short antisense transcripts. Interestingly, the antisense RNA-mediated deposition of inactive chromatin-specific histone modifications was higher with the longer antisense transcripts than with the shorter antisense transcripts. The kinetic studies of expression and chromatin remodeling of overlapping and nonoverlapping genes in response to antisense transcription revealed that the overlapping gene was rapidly silenced due to decrease in the occupancy of basal transcription machinery and simultaneous enrichment of its promoter with inactive chromatin modifications. The nonoverlapping gene, initially enriched with histone modifications specific to active chromatin, was subsequently silenced. Surprisingly, the flanking sequences were initially enriched with H3K9 monomethylation, as compared to di- and trimethylation, with a subsequent shift to trimethylated H3K9 enrichment. Our data provide a new perspective into antisense RNA-mediated gene silencing, and, more importantly, provide an explanation for why the antisense transcripts encoded from imprinting control regions are of significant length.
连接反义RNA、染色质结构和基因表达的潜在机制尚未完全阐明。在此我们表明，由Kcnq1ot1反义启动子编码的长转录本比短反义转录本更有效地沉默侧翼基因。有趣的是，与较短的反义转录本相比，较长的反义转录本介导的无活性染色质特异性组蛋白修饰的沉积更高。对重叠和非重叠基因响应反义转录的表达和染色质重塑的动力学研究表明，由于基础转录机制的占据减少以及其启动子同时富集无活性染色质修饰，重叠基因迅速沉默。非重叠基因最初富含活性染色质特有的组蛋白修饰，随后被沉默。令人惊讶的是，与二甲基化和三甲基化相比，侧翼序列最初富含H3K9单甲基化，随后转变为三甲基化的H3K9富集。我们的数据为反义RNA介导的基因沉默提供了新的视角，更重要的是，解释了为什么从印记控制区域编码的反义转录本具有显著的长度。
