RNA pol II Dynamics Modulate Co-transcriptional Chromatin Modification, CTD phosphorylation and transcriptional direction

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.本研究利用人源细胞中的RNA聚合酶II（RNA polymerase II, Pol II）突变体，发现转录速率减慢会重定位特定的共转录沉积染色质修饰：组蛋白H3赖氨酸36三甲基化（H3K36me3）在基因内向5'端偏移，而组蛋白H3赖氨酸4二甲基化（H3K4me2）则向转录起始位点上游进一步延伸。转录速率减慢还会诱导基因5'端的羧基末端结构域丝氨酸2（CTD Ser2）位点发生高度磷酸化，该现象在酵母中保守存在。我们提出了“靶区停留时间”（dwell-time in the target zone）模型，用以阐释转录动态对共转录沉积蛋白质修饰建立过程的调控效应。启动子近端的丝氨酸2磷酸化与转录起始位点处更长的Pol II停留时间相关，同时由于启动子区域反向反义转录被显著增强，该修饰还会降低转录极性。