English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The Cdk8 kinase module regulates interaction of the mediator complex with RNA polymerase II

Osman, S., Mohammad, E., Lidschreiber, M., Stuetzer, A., Bazsó, F. L., Maier, K. C., et al. (2021). The Cdk8 kinase module regulates interaction of the mediator complex with RNA polymerase II. Journal of Biological Chemistry, 296: 100734. doi:10.1016/j.jbc.2021.100734.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files
hide Files
:
3343677.pdf (Publisher version), 3MB
Name:
3343677.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-

Locators

show

Creators

show
hide
 Creators:
Osman, S.1, Author              
Mohammad, E.1, Author              
Lidschreiber, M.1, Author              
Stuetzer, A.2, Author              
Bazsó, F. L.3, Author              
Maier, K. C.1, Author              
Urlaub, H.2, Author              
Cramer, P.1, Author              
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              
2Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              
3Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              

Content

show
hide
Free keywords: mediator; Cdk8 kinase module; transcription initiation; gene activation; gene regulation
 Abstract: The Cdk8 kinase module (CKM) is a dissociable part of the coactivator complex mediator, which regulates gene transcription by RNA polymerase II. The CKM has both negative and positive functions in gene transcription that remain poorly understood at the mechanistic level. In order to reconstitute the role of the CKM in transcription initiation, we prepared recombinant CKM from the yeast Saccharomyces cerevisiae. We showed that CKM bound to the core mediator (cMed) complex, sterically inhibiting cMed from binding to the polymerase II preinitiation complex (PIC) in vitro. We further showed that the Cdk8 kinase activity of the CKM weakened CKM–cMed interaction, thereby facilitating dissociation of the CKM and enabling mediator to bind the PIC in order to stimulate transcription initiation. Finally, we report that the kinase activity of Cdk8 is required for gene activation during the stressful condition of heat shock in vivo but not under steady-state growth conditions. Based on these results, we propose a model in which the CKM negatively regulates mediator function at upstream-activating sequences by preventing mediator binding to the PIC at the gene promoter. However, during gene activation in response to stress, the Cdk8 kinase activity of the CKM may release mediator and allow its binding to the PIC, thereby accounting for the positive function of CKM. This may impart improved adaptability to stress by allowing a rapid transcriptional response to environmental changes, and we speculate that a similar mechanism in metazoans may allow the precise timing of developmental transcription programs.

Details

show
hide
Language(s): eng - English
 Dates: 2021-04-292021-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.jbc.2021.100734
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Biological Chemistry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: 16 Volume / Issue: 296 Sequence Number: 100734 Start / End Page: - Identifier: -