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

Seiji Yamamoto, Tomoko Hagihara, Yoshiyuki Horiuchi, Akira Okui, Shotaro Wani, Tokuyuki Yoshida, Takao Inoue, Aki Tanaka, Takashi Ito, Yutaka Hirose, Yoshiaki Ohkuma

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)265-276
Number of pages12
JournalGenes to Cells
Volume22
Issue number3
DOIs
Publication statusPublished - Mar 1 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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