Promoter-proximal RNA polymerase II termination regulates transcription during human cell type transition

Metazoan gene transcription by RNA polymerase (Pol) II is regulated in the promoter-proximal region. Pol II can undergo termination in the promoter-proximal region, but whether this can contribute to transcription regulation in cells remains unclear. Here, we extend our previous multi-omics analysis to quantify changes in transcription kinetics during a human cell type transition event. We observe that upregulation of transcription involves an increase in initiation frequency and, at a set of genes, a decrease in promoter-proximal termination. In turn, downregulation of transcription involves a decrease in initiation frequency and an increase in promoter-proximal termination. Thus, promoter-proximal termination of Pol II contributes to the regulation of human gene transcription. mNET-seq, ChIP-nexus, ChIP-seq TT-seq of publicly available samples were re-analyzed from GSE131620: GSM3791280, SRX8272956, SAMN11822484, TT_0h_rep1 GSM3791281, SRX8272902, SAMN11822483, TT_0h_rep2 GSM3791282, SRX8272903, SAMN11822482, TT_12h_rep1 GSM3791283, SRX8272904, SAMN11822481, TT_12h_rep2 GSM3791284, SRX8272905, SAMN11822480, TT_24h_rep1 GSM3791285, SRX8272906, SAMN11822479, TT_24h_rep2 GSM3791290, SRX8272911, SAMN11822474, TT_72h_rep1 GSM3791291, SRX8272912, SAMN11822473, TT_72h_rep2 GSM3791292, SRX8272913, SAMN11822472, TT_96h_rep1 GSM3791293, SRX8272914, SAMN11822471, TT_96h_rep2

RNA聚合酶II（RNA polymerase II, Pol II）介导的后生动物基因转录，在启动子近端区域受到调控。Pol II可在该区域发生转录终止，但这一过程是否能够参与细胞内的转录调控，目前仍不明确。
本研究拓展此前的多组学分析策略，对人类细胞类型转换过程中转录动力学的变化进行定量检测。研究发现，转录上调过程伴随转录起始频率的提升，且在部分基因中，启动子近端区域的终止事件发生率显著降低；反之，转录下调则伴随起始频率下降与启动子近端终止事件发生率的升高。由此可见，Pol II的启动子近端终止过程参与了人类基因转录的调控。
本研究对公开获取的mNET-seq、ChIP-nexus、ChIP-seq及TT-seq样本数据进行重新分析，所有数据均来自GSE131620数据集，具体样本如下：
TT_0h_rep1：GSM3791280、SRX8272956、SAMN11822484；
TT_0h_rep2：GSM3791281、SRX8272902、SAMN11822483；
GSM3791282、SRX8272903、SAMN11822482；
TT_12h_rep1：GSM3791283、SRX8272904、SAMN11822481；
TT_12h_rep2：GSM3791284、SRX8272905、SAMN11822480；
TT_24h_rep1：GSM3791285、SRX8272906、SAMN11822479；
TT_24h_rep2：GSM3791290、SRX8272911、SAMN11822474；
TT_72h_rep1：GSM3791291、SRX8272912、SAMN11822473；
TT_72h_rep2：GSM3791292、SRX8272913、SAMN11822472；
TT_96h_rep1：GSM3791293、SRX8272914、SAMN11822471；
TT_96h_rep2