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oai:repisalud.isciii.es:20.500.12105/253192025-12-18T13:01:40Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Herrero-Ruiz, Andrés author Martínez-García, Pedro Manuel author Terrón-Bautista, José author Millán-Zambrano, Gonzalo author Lieberman, Jenna Ariel author Jimeno-González, Silvia author Cortes-Ledesma, Felipe author 2021-04-13 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 describe the control of promoter-proximal pausing by TOP2A as a layer for the regulation of gene expression, which can act as a molecular switch to rapidly activate transcription, possibly by regulating the accumulation of DNA supercoiling at promoter regions. Cell Rep . 2021 Apr 13;35(2):108977 https://hdl.handle.net/20.500.12105/25319 33852840 Cell Rep DNA supercoiling DNA topoisomerases DNA topology gene expression promoter-proximal pausing transcription elongation Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing.