2026-04-29T07:22:11Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/253192025-12-18T13:01:40Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Asociacion Española contra el Cáncer
2024-10-28T10:18:46Z
2024-10-28T10:18:46Z
2021-04-13
Cell Rep . 2021 Apr 13;35(2):108977
https://hdl.handle.net/20.500.12105/25319
33852840
Cell Rep
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.
eng
DNA supercoiling
DNA topoisomerases
DNA topology
gene expression
promoter-proximal pausing
transcription elongation
Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing.
research article
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URL
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File
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TopoisomeraseIIarepresses-2021.pdf
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text/plain
TopoisomeraseIIarepresses-2021.pdf.txt