Topoisomerase IIα represses transcription by enforcing promoter-proximal pausing.
Cell Rep
; 35(2): 108977, 2021 04 13.
Article
in En
| MEDLINE
| ID: mdl-33852840
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 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
RNA Polymerase II
/
DNA, Superhelical
/
Proto-Oncogene Proteins c-fos
/
DNA Topoisomerases, Type II
/
Poly-ADP-Ribose Binding Proteins
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2021
Type:
Article
Affiliation country:
Spain