---
_id: '599'
abstract:
- lang: eng
text: The human CDK8 subcomplex (CDK8, cyclin C, Med12, and Med13) negatively regulates
transcription in ways not completely defined; past studies suggested CDK8 kinase
activity was required for its repressive function. Using a reconstituted transcription
system together with recombinant or endogenous CDK8 subcomplexes, we demonstrate
that, in fact, Med12 and Med13 are critical for subcomplex-dependent repression,
whereas CDK8 kinase activity is not. A hallmark of activated transcription is
efficient reinitiation from promoter-bound scaffold complexes that recruit a series
of pol II enzymes to the gene. Notably, the CDK8 submodule strongly represses
even reinitiation events, suggesting a means to fine tune transcript levels. Structural
and biochemical studies confirm the CDK8 submodule binds the Mediator leg/tail
domain via the Med13 subunit, and this submodule-Mediator association precludes
pol II recruitment. Collectively, these results reveal the CDK8 subcomplex functions
as a simple switch that controls the Mediator-pol II interaction to help regulate
transcription initiation and reinitiation events. As Mediator is generally required
for expression of protein-coding genes, this may reflect a common mechanism by
which activated transcription is shut down in human cells.
article_processing_charge: No
author:
- first_name: Matthew
full_name: Knuesel, Matthew
last_name: Knuesel
- first_name: Krista
full_name: Meyer, Krista
last_name: Meyer
- first_name: Carrie A
full_name: Bernecky, Carrie A
id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
last_name: Bernecky
orcid: 0000-0003-0893-7036
- first_name: Dylan
full_name: Taatjes, Dylan
last_name: Taatjes
citation:
ama: Knuesel M, Meyer K, Bernecky C, Taatjes D. The human CDK8 subcomplex is a molecular
switch that controls Mediator coactivator function. Genes and Development.
2009;23(4):439-451. doi:10.1101/gad.1767009
apa: Knuesel, M., Meyer, K., Bernecky, C., & Taatjes, D. (2009). The human CDK8
subcomplex is a molecular switch that controls Mediator coactivator function.
Genes and Development. Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/gad.1767009
chicago: Knuesel, Matthew, Krista Meyer, Carrie Bernecky, and Dylan Taatjes. “The
Human CDK8 Subcomplex Is a Molecular Switch That Controls Mediator Coactivator
Function.” Genes and Development. Cold Spring Harbor Laboratory Press,
2009. https://doi.org/10.1101/gad.1767009.
ieee: M. Knuesel, K. Meyer, C. Bernecky, and D. Taatjes, “The human CDK8 subcomplex
is a molecular switch that controls Mediator coactivator function,” Genes and
Development, vol. 23, no. 4. Cold Spring Harbor Laboratory Press, pp. 439–451,
2009.
ista: Knuesel M, Meyer K, Bernecky C, Taatjes D. 2009. The human CDK8 subcomplex
is a molecular switch that controls Mediator coactivator function. Genes and Development.
23(4), 439–451.
mla: Knuesel, Matthew, et al. “The Human CDK8 Subcomplex Is a Molecular Switch That
Controls Mediator Coactivator Function.” Genes and Development, vol. 23,
no. 4, Cold Spring Harbor Laboratory Press, 2009, pp. 439–51, doi:10.1101/gad.1767009.
short: M. Knuesel, K. Meyer, C. Bernecky, D. Taatjes, Genes and Development 23 (2009)
439–451.
date_created: 2018-12-11T11:47:25Z
date_published: 2009-02-15T00:00:00Z
date_updated: 2021-01-12T08:05:32Z
day: '15'
doi: 10.1101/gad.1767009
extern: '1'
intvolume: ' 23'
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648653/
month: '02'
oa: 1
oa_version: None
page: 439 - 451
publication: Genes and Development
publication_status: published
publisher: Cold Spring Harbor Laboratory Press
publist_id: '7211'
status: public
title: The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator
function
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2009'
...