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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
Author(s) -
Yamamoto Seiji,
Hagihara Tomoko,
Horiuchi Yoshiyuki,
Okui Akira,
Wani Shotaro,
Yoshida Tokuyuki,
Inoue Takao,
Tanaka Aki,
Ito Takashi,
Hirose Yutaka,
Ohkuma Yoshiaki
Publication year - 2017
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12475
Subject(s) - biology , mediator , microbiology and biotechnology , rna polymerase ii , cyclin dependent kinase , cyclin dependent kinase 8 , general transcription factor , promoter , cancer research , signal transduction , gene , gene expression , genetics , cell cycle , notch signaling pathway
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.