Mediator cyclin‐dependent kinases upregulate transcription of inflammatory genes in cooperation with NF ‐κB and C/ EBP β on stimulation of Toll‐like receptor 9

In eukaryotes, the Mediator complex has important roles in regulation of transcription by RNA polymerase II . Mediator is a large complex with more than 20 subunits that form head, middle, tail and CDK /cyclin modules. Among them, CDK 8 and/or CDK 19 ( CDK 8/19), and their counterpart cyclin C, form the CDK /cyclin module together with Mediator subunits MED 12 and MED 13. Despite evidences of both activation and repression, the precise functional roles of CDK 8/19 in transcription are still elusive. Our previous results indicate that CDK 8/19 recruits epigenetic regulators to repress immunoresponse genes. Here, this study focused on Toll‐like receptors ( TLR s), which exert innate immune responses through recognition of pathogen‐associated molecular patterns and examined the functional roles of CDK 8/19. As a result, CDK 8/19 regulated transcription of inflammatory genes on stimulation of TLR 9 in myeloma‐derived RPMI 8226 cells, which led to expression of inflammation‐associated genes such as IL 8 , IL 10 , PTX 3 and CCL 2 . Mediator subunits CDK 8/19 and MED 1, inflammation‐related transcriptional activator NF ‐κB and C/ EBP β, and general transcription factors TFIIE and TFIIB colocalized at the promoter regions of these genes under this condition. Our results show that CDK 8/19 positively regulates inflammatory gene transcription in cooperation with NF ‐κB and C/ EBP β on stimulation of TLR 9.