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

Kseniia Lysakovskaia, Arjun Devadas, Björn Schwalb, Michael Lidschreiber, Patrick Cramer

2025Nature Structural & Molecular Biology14 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

Transcription (linguistics)RNA polymerase IIPromoterGeneral transcription factorMolecular biologyBiologyTAF2Transcription factor II DTranscriptional regulationResponse elementTranscription factor II FE-boxGeneRNA polymerase IIICell biologyRNA polymeraseTranscription factorGene expressionRNAGeneticsLinguisticsPhilosophyGenomics and Chromatin DynamicsRNA Research and SplicingRNA and protein synthesis mechanisms