--- _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' ...