RT Journal Article
T1 Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing
A1 Herrero-Ruiz, Andrés
A1 Martínez-García, Pedro Manuel
A1 Terrón-Bautista, José
A1 Millán-Zambrano, Gonzalo
A1 Lieberman, Jenna Ariel
A1 Jimeno-González, Silvia
A1 Cortés-Ledesma, Felipe
K1 DNA supercoiling
K1 DNA topoisomerases
K1 DNA topology
K1 Gene expression
K1 Promoter-proximal pausing
K1 Transcription elongation
K1 ADN-topoisomerasas
K1 Expresión génica
K1 Elongación de la transcripción genética
AB 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.
PB Cell Press
YR 2021
FD 2021-04-13
LK http://hdl.handle.net/10668/3655
UL http://hdl.handle.net/10668/3655
LA en
NO Herrero-Ruiz A, Martínez-García PM, Terrón-Bautista J, Millán-Zambrano G, Lieberman JA, Jimeno-González S, et al. Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing. Cell Rep. 2021 Apr 13;35(2):108977
DS RISalud
RD Apr 7, 2025