{"title":"The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function","_id":"599","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648653/","open_access":"1"}],"doi":"10.1101/gad.1767009","author":[{"last_name":"Knuesel","full_name":"Knuesel, Matthew","first_name":"Matthew"},{"last_name":"Meyer","full_name":"Meyer, Krista","first_name":"Krista"},{"orcid":"0000-0003-0893-7036","first_name":"Carrie A","full_name":"Bernecky, Carrie A","id":"2CB9DFE2-F248-11E8-B48F-1D18A9856A87","last_name":"Bernecky"},{"first_name":"Dylan","full_name":"Taatjes, Dylan","last_name":"Taatjes"}],"oa_version":"None","abstract":[{"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.","lang":"eng"}],"publication":"Genes and Development","publication_status":"published","issue":"4","extern":"1","type":"journal_article","publist_id":"7211","date_updated":"2021-01-12T08:05:32Z","volume":23,"language":[{"iso":"eng"}],"intvolume":"        23","day":"15","publisher":"Cold Spring Harbor Laboratory Press","year":"2009","status":"public","page":"439 - 451","oa":1,"date_published":"2009-02-15T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","month":"02","date_created":"2018-12-11T11:47:25Z","citation":{"apa":"Knuesel, M., Meyer, K., Bernecky, C., &#38; Taatjes, D. (2009). The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function. <i>Genes and Development</i>. Cold Spring Harbor Laboratory Press. <a href=\"https://doi.org/10.1101/gad.1767009\">https://doi.org/10.1101/gad.1767009</a>","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.","chicago":"Knuesel, Matthew, Krista Meyer, Carrie Bernecky, and Dylan Taatjes. “The Human CDK8 Subcomplex Is a Molecular Switch That Controls Mediator Coactivator Function.” <i>Genes and Development</i>. Cold Spring Harbor Laboratory Press, 2009. <a href=\"https://doi.org/10.1101/gad.1767009\">https://doi.org/10.1101/gad.1767009</a>.","ieee":"M. Knuesel, K. Meyer, C. Bernecky, and D. Taatjes, “The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function,” <i>Genes and Development</i>, vol. 23, no. 4. Cold Spring Harbor Laboratory Press, pp. 439–451, 2009.","mla":"Knuesel, Matthew, et al. “The Human CDK8 Subcomplex Is a Molecular Switch That Controls Mediator Coactivator Function.” <i>Genes and Development</i>, vol. 23, no. 4, Cold Spring Harbor Laboratory Press, 2009, pp. 439–51, doi:<a href=\"https://doi.org/10.1101/gad.1767009\">10.1101/gad.1767009</a>.","ama":"Knuesel M, Meyer K, Bernecky C, Taatjes D. The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function. <i>Genes and Development</i>. 2009;23(4):439-451. doi:<a href=\"https://doi.org/10.1101/gad.1767009\">10.1101/gad.1767009</a>","short":"M. Knuesel, K. Meyer, C. Bernecky, D. Taatjes, Genes and Development 23 (2009) 439–451."}}