Abstract：
N6-methyladenosine modification (m6A) fine-tunes RNA fate in a variety of ways, thus regulating multiple fundamental biological processes. m6A writers bind to chromatin and interact with RNA polymerase II (RNAPII) during transcription. To evaluate how the dynamics of the transcription process impact m6A deposition, we studied RNAPII elongation rates in mouse embryonic stem cells with altered chromatin configurations, due to reductions in linker histone H1 content. We found that genes transcribed at slow speed are preferentially methylated and display unique signatures at their promoter region, namely high levels of histone H1, together with marks of bivalent chromatin and low RNAPII pausing. They are also highly susceptible to m6A loss upon histone H1 reduction. These results indicate that RNAPII velocity links chromatin structure and the deposition of m6A, highlighting the intricate relationship between different regulatory layers on nascent mRNA molecules.
摘要：
N6-甲基腺苷修饰（m6A）以多种方式微调RNA命运，从而调节多个基本的生物过程。m6A作者在转录过程中与染色质结合并与RNA聚合酶II（RNAPII）相互作用。为了评估转录过程的动力学如何影响m6A沉积，我们研究了染色质构型改变的小鼠胚胎干细胞的RNAPII伸长率，由于接头组蛋白H1含量的减少。我们发现以慢速度转录的基因优先被甲基化，并在其启动子区域显示出独特的特征。即高水平的组蛋白H1，以及二价染色质的标记和低RNAPII暂停。它们在组蛋白H1减少时也高度易受m6A损失的影响。这些结果表明RNAPII速度连接染色质结构和m6A的沉积，突出了新生mRNA分子上不同调控层之间的复杂关系。
