Mediator cyclin ‐dependent kinases upregulate transcription of inflammatory genes in cooperation with NF‐κB and C/EBPβ 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, CDK8 and/or CDK19 (CDK8/19), and their counterpart cyclin C, form the CDK/cyclin module together with Mediator subunits MED12 and MED13. Despite evidences of both activation and repression, the precise functional roles of CDK8/19 in transcription are still elusive. Our previous results indicate that CDK8/19 recruits epigenetic regulators to repress immunoresponse genes. Here, this study focused on Toll‐like receptors (TLRs), which exert innate immune responses through recognition of pathogen‐associated molecular patterns and examined the functional roles of CDK8/19. As a result, CDK8/19 regulated transcription of inflammatory genes on stimulation of TLR9 in myeloma‐derived RPMI8226 cells, which led to expression of inflammation‐associated genes such as IL8, IL10, PTX3 and CCL2. Mediator subunits CDK8/19 and MED1, inflammation‐related transcriptional activator NF‐κB and C/EBPβ, and general transcription factors TFIIE and TFIIB colocalized at the promoter regions of these genes under this condition. Our results show that CDK8/19 positively regulates inflammatory gene transcription in cooperation with NF‐κB and C/EBPβ on stimulation of TLR9.

Here the present study focused on Toll‐like receptors (TLRs), which exert innate immune respo...

Source: Genes to Cells - December 31, 2016 Category: Genetics & Stem Cells Authors: Seiji Yamamoto, Tomoko Hagihara, Yoshiyuki Horiuchi, Akira Okui, Shotaro Wani, Tokuyuki Yoshida, Takao Inoue, Aki Tanaka, Takashi Ito, Yutaka Hirose, Yoshiaki Ohkuma Tags: Original Article Source Type: research