RNA Pol II Dynamics Modulate Co-transcriptional Chromatin Modification, CTD Phosphorylation, and Transcriptional Direction.
RNA Pol II Dynamics Modulate Co-transcriptional Chromatin Modification, CTD Phosphorylation, and Transcriptional Direction.
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DOI：
10.1016/j.molcel.2017.04.016
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发表时间：
2017-05-18
期刊：
影响因子：
16
通讯作者：
Bentley DL
中科院分区：
文献类型：
--
作者：
Fong N;Saldi T;Sheridan RM;Cortazar MA;Bentley DL
真核基因是通过在RNA、PolII、CTD和染色质模板上保守的翻译后修饰来标记的。这些标记的5‘-3’轮廓是如何建立的，目前还知之甚少。在人类细胞中使用polII突变体，我们发现慢转录重新定位了特定的共转录沉积的染色质修饰；H3K36me3在基因内向5‘端移动，H3K4me2进一步延伸到起始点的上游。慢转录还会引起酵母中保守基因5‘端CTD Ser2残基的过度磷酸化。我们提出了一个“靶区停留时间”模型来解释转录动力学对共转录沉积蛋白修饰的影响。启动子-近端Ser2的磷酸化与PolII在起始点的停留时间延长和转录极性降低有关，这是由于强烈增强了启动子上的发散反义转录。这些结果表明，PolII动力学有助于控制正义和发散反义转录之间的决定。
Eukaryotic genes are marked by conserved post-translational modifications on the RNA pol II CTD and the chromatin template. How the 5′–3′ profiles of these marks are established is poorly understood. Using pol II mutants in human cells we found that slow transcription repositioned specific co-transcriptionally deposited chromatin modifications; H3K36me3 shifted within genes toward 5′ ends and H3K4me2 extended further upstream of start sites. Slow transcription also evoked a hyperphosphorylation of CTD Ser2 residues at 5′ ends of genes that is conserved in yeast. We propose a “dwell-time in the target zone” model to explain the effects of transcriptional dynamics on establishment of co-transcriptionally deposited protein modifications. Promoter-proximal Ser2 phosphorylation is associated with longer pol II dwell time at start sites and reduced transcriptional polarity due to strongly enhanced divergent antisense transcription at promoters. These results demonstrate that pol II dynamics help govern the decision between sense and divergent antisense transcription.