Transcription-coupled changes to chromatin underpin gene silencing by transcriptional interference.
Transcription-coupled changes to chromatin underpin gene silencing by transcriptional interference.
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DOI：
10.1093/nar/gkw801
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发表时间：
2016-12-15
影响因子：
14.9
通讯作者：
Allshire RC
中科院分区：
文献类型：
--
作者：
Ard R;Allshire RC
长的非编码RNA(LncRNA)转录到下游启动子经常会导致转录干扰。然而，这种压制的机制还没有完全被理解。我们最近发现裂殖酵母对药物的耐受性是由tgp1+渗透酶基因上游的lncRNA转录控制的。在这里，我们证明了tgp1+的转录干扰涉及到由保守的延伸因子Set2、Clr6CII、Spt6和FACT介导的几个转录偶联染色质变化。众所周知，这些因子与RNAPII一起旅行，并建立抑制染色质，以限制存在于基因体中的隐蔽启动子的异常转录启动。因此，我们得出结论，RNAPII相关的保守机制既可以在基因转录过程中抑制基因内的隐蔽启动子，也可以通过转录干扰来抑制基因启动子。我们的分析还表明，转录干扰的关键机制特征在S.pombe和高度分化的芽生酵母酿酒酵母之间是相同的。因此，转录干扰是一种古老的、保守的严密控制基因表达的机制。我们的机械洞察力使我们能够预测和验证涉及S.pombe Pho1+基因的转录干扰的第二个例子。鉴于真核基因组是普遍转录的，转录干扰可能代表了比目前所认识的更普遍的基因调控特征。
Long non-coding RNA (lncRNA) transcription into a downstream promoter frequently results in transcriptional interference. However, the mechanism of this repression is not fully understood. We recently showed that drug tolerance in fission yeast Schizosaccharomyces pombe is controlled by lncRNA transcription upstream of the tgp1+ permease gene. Here we demonstrate that transcriptional interference of tgp1+ involves several transcription-coupled chromatin changes mediated by conserved elongation factors Set2, Clr6CII, Spt6 and FACT. These factors are known to travel with RNAPII and establish repressive chromatin in order to limit aberrant transcription initiation from cryptic promoters present in gene bodies. We therefore conclude that conserved RNAPII-associated mechanisms exist to both suppress intragenic cryptic promoters during genic transcription and to repress gene promoters by transcriptional interference. Our analyses also demonstrate that key mechanistic features of transcriptional interference are shared between S. pombe and the highly divergent budding yeast Saccharomyces cerevisiae. Thus, transcriptional interference is an ancient, conserved mechanism for tightly controlling gene expression. Our mechanistic insights allowed us to predict and validate a second example of transcriptional interference involving the S. pombe pho1+ gene. Given that eukaryotic genomes are pervasively transcribed, transcriptional interference likely represents a more general feature of gene regulation than is currently appreciated.
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RNA在意外的地方：长的非编码RNA在不同的细胞环境中起作用。
DOI：
10.1038/nrm3679
发表时间：
2013-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Geisler S;Coller J
通讯作者：
Coller J
影响因子：
7.7
作者：
Bassett AR;Akhtar A;Barlow DP;Bird AP;Brockdorff N;Duboule D;Ephrussi A;Ferguson-Smith AC;Gingeras TR;Haerty W;Higgs DR;Miska EA;Ponting CP
通讯作者：
Ponting CP
影响因子：
4.5
作者：
Drouin S;Laramée L;Jacques PÉ;Forest A;Bergeron M;Robert F
通讯作者：
Robert F
影响因子：
30.3
作者：
Han Y;Lin YB;An W;Xu J;Yang HC;O'Connell K;Dordai D;Boeke JD;Siliciano JD;Siliciano RF
通讯作者：
Siliciano RF
影响因子：
64.5
作者：
Carrozza, MJ;Li, B;Workman, JL
通讯作者：
Workman, JL