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

Metazoan gene transcription by RNA polymerase II (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 multiomics 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. Lysakovskaia et al. use a multiomics approach to investigate promoter-proximal termination of RNA polymerase II and show that it is a regulated process that can contribute to both upregulation and downregulation of genes during a human cell type transition event.