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. Overall design: 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