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

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