DOI: 10.1101/gad.1767009. The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function

The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function

10.1101/gad.1767009

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

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.

Bibliography

Knuesel, M. T., Meyer, K. D., Bernecky, C., & Taatjes, D. J. (2009). The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function. Genes & Development, 23(4), 439â451.

Authors 4

Matthew T. Knuesel (first)
Krista D. Meyer (additional)
Carrie Bernecky (additional)
Dylan J. Taatjes (additional)

References 54 Referenced 295

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Dates

Type	When
Created	16 years, 5 months ago (Feb. 24, 2009, 8:57 a.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, 12:21 p.m.)
Indexed	1 week, 2 days ago (Aug. 12, 2025, 6:08 p.m.)
Issued	16 years, 6 months ago (Feb. 15, 2009)
Published	16 years, 6 months ago (Feb. 15, 2009)
Published Online	16 years, 5 months ago (Feb. 24, 2009)
Published Print	16 years, 6 months ago (Feb. 15, 2009)

Funders 0

None

BibTeX

@article{Knuesel_2009, title={The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function}, volume={23}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1767009}, DOI={10.1101/gad.1767009}, number={4}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Knuesel, Matthew T. and Meyer, Krista D. and Bernecky, Carrie and Taatjes, Dylan J.}, year={2009}, month=feb, pages={439–451} }

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