Local potentiation of stress-responsive genes by upstream noncoding transcription.
Local potentiation of stress-responsive genes by upstream noncoding transcription.
复制标题
DOI：
10.1093/nar/gkw142
复制
发表时间：
2016-06-20
影响因子：
14.9
通讯作者：
Ohta K
中科院分区：
文献类型：
--
作者：
Takemata N;Oda A;Yamada T;Galipon J;Miyoshi T;Suzuki Y;Sugano S;Hoffman CS;Hirota K;Ohta K
人们一直认为，大量的长链非编码rna （lncrna）参与基因调控。在裂变酵母中，葡萄糖饥饿触发lncRNA在包括fbp1（果糖-1,6-双磷酸酶1）在内的应激反应基因的启动子区域进行转录。在fbp1启动子处，该转录促进染色质重塑和fbp1 mRNA表达。在这里，我们证明了这种上游非编码转录促进了应激响应转录激活子Atf1在转录位点的启动子关联，从而导致下游应激基因的激活。全基因组分析显示，当细胞用转录抑制剂处理时，约50个Atf1结合位点显示Atf1占用显著减少。正如在fbp1中观察到的那样，大多数这些转录增强的atf1结合位点与邻近mrna或lncrna的胁迫依赖性诱导有关。这些Atf1结合位点在富含葡萄糖的条件下表现出低Atf1占用率和高组蛋白密度，并且在葡萄糖消耗后染色质状态发生戏剧性变化：增强Atf1结合，组蛋白排出和组蛋白H3乙酰化。我们还发现，上游转录物与Groucho-Tup1型转录共抑制因子Tup11和Tup12结合，并局部拮抗它们对Atf1结合的抑制功能。这些结果揭示了上游非编码转录通过协同抑制子的对抗局部放大胁迫诱导基因特异性激活的新机制。
It has been postulated that a myriad of long noncoding RNAs (lncRNAs) contribute to gene regulation. In fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1). At the fbp1 promoter, this transcription promotes chromatin remodeling and fbp1 mRNA expression. Here, we demonstrate that such upstream noncoding transcription facilitates promoter association of the stress-responsive transcriptional activator Atf1 at the sites of transcription, leading to activation of the downstream stress genes. Genome-wide analyses revealed that ∼50 Atf1-binding sites show marked decrease in Atf1 occupancy when cells are treated with a transcription inhibitor. Most of these transcription-enhanced Atf1-binding sites are associated with stress-dependent induction of the adjacent mRNAs or lncRNAs, as observed in fbp1. These Atf1-binding sites exhibit low Atf1 occupancy and high histone density in glucose-rich conditions, and undergo dramatic changes in chromatin status after glucose depletion: enhanced Atf1 binding, histone eviction, and histone H3 acetylation. We also found that upstream transcripts bind to the Groucho-Tup1 type transcriptional corepressors Tup11 and Tup12, and locally antagonize their repressive functions on Atf1 binding. These results reveal a new mechanism in which upstream noncoding transcription locally magnifies the specific activation of stress-inducible genes via counteraction of corepressors.