The pause-initiation limit restricts transcription activation in human cells.
Cell Survival
Cyclin-Dependent Kinase 9
/ metabolism
Gene Expression Regulation
Genome
HSP70 Heat-Shock Proteins
/ genetics
Humans
K562 Cells
Kinetics
Positive Transcriptional Elongation Factor B
/ metabolism
RNA Polymerase II
/ metabolism
Transcription, Genetic
Transcriptional Activation
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 08 2019
09 08 2019
Historique:
received:
21
01
2019
accepted:
18
07
2019
entrez:
11
8
2019
pubmed:
11
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
Eukaryotic gene transcription is often controlled at the level of RNA polymerase II (Pol II) pausing in the promoter-proximal region. Pausing Pol II limits the frequency of transcription initiation ('pause-initiation limit'), predicting that the pause duration must be decreased for transcriptional activation. To test this prediction, we conduct a genome-wide kinetic analysis of the heat shock response in human cells. We show that the pause-initiation limit restricts transcriptional activation at most genes. Gene activation generally requires the activity of the P-TEFb kinase CDK9, which decreases the duration of Pol II pausing and thereby enables an increase in the productive initiation frequency. The transcription of enhancer elements is generally not pause limited and can be activated without CDK9 activity. Our results define the kinetics of Pol II transcriptional regulation in human cells at all gene classes during a natural transcription response.
Identifiants
pubmed: 31399571
doi: 10.1038/s41467-019-11536-8
pii: 10.1038/s41467-019-11536-8
pmc: PMC6689055
doi:
Substances chimiques
HSP70 Heat-Shock Proteins
0
Positive Transcriptional Elongation Factor B
EC 2.7.11.-
CDK9 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 9
EC 2.7.11.22
RNA Polymerase II
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3603Références
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