Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing.

ABSTRACT: Accumulation of topological stress in the form of DNA supercoiling is inherent to the advance of RNA polymerase II (Pol II) and needs to be resolved by DNA topoisomerases to sustain productive transcriptional elongation. Topoisomerases are therefore considered positive facilitators of transcription. Here, we show that, in contrast to this general assumption, human topoisomerase IIα (TOP2A) activity at promoters represses transcription of immediate early genes such as c-FOS, maintaining them under basal repressed conditions. Thus, TOP2A inhibition creates a particular topological context that results in rapid release from promoter-proximal pausing and transcriptional upregulation, which mimics the typical bursting behavior of these genes in response to physiological stimulus. We therefore d

SUBMITTER: Herrero-Ruiz A 

PROVIDER: S-EPMC8052185 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature