Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9.
CDK9
INTS11
Integrator
RNA polymerase II
chromosomes
cleavage and polyadenylation
gene expression
human
promoter
transcription
transcription initiation
transcription termination
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
08 Jul 2024
08 Jul 2024
Historique:
medline:
8
7
2024
pubmed:
8
7
2024
entrez:
8
7
2024
Statut:
epublish
Résumé
RNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient than in the antisense direction, which establishes initial promoter directionality. After transcription begins, the opposing functions of the endonucleolytic subunit of Integrator, INTS11, and cyclin-dependent kinase 9 (CDK9) maintain directionality. Specifically, INTS11 terminates antisense transcription, whereas sense transcription is protected from INTS11-dependent attenuation by CDK9 activity. Strikingly, INTS11 attenuates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 desensitises transcription to INTS11. Therefore, the preferential initiation of sense transcription and the opposing activities of CDK9 and INTS11 explain mammalian promoter directionality.
Identifiants
pubmed: 38976490
doi: 10.7554/eLife.92764
pii: 92764
doi:
pii:
Substances chimiques
Cyclin-Dependent Kinase 9
EC 2.7.11.22
CDK9 protein, human
EC 2.7.11.22
SUPT5H protein, human
0
RNA Polymerase II
EC 2.7.7.-
Nuclear Proteins
0
Transcriptional Elongation Factors
0
Banques de données
GEO
['GSE243266']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
ID : 10.35802/223106
Pays : United Kingdom
Informations de copyright
© 2024, Eaton, Board et al.
Déclaration de conflit d'intérêts
JE, JB, LD, CE, SW No competing interests declared
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