Cyclin-dependent kinase 8 module expression profiling reveals requirement of mediator subunits 12 and 13 for transcription of Serpent-dependent innate immunity genes in Drosophila.
The Cdk8 (cyclin-dependent kinase 8) module of Mediator integrates regulatory cues from transcription factors to RNA polymerase II. It consists of four subunits where Med12 and Med13 link Cdk8 and cyclin C (CycC) to core Mediator. Here we have investigated the contributions of the Cdk8 module subunits to transcriptional regulation using RNA interference in Drosophila cells. Genome-wide expression profiling demonstrated separation of Cdk8-CycC and Med12-Med13 profiles. However, transcriptional regulation by Cdk8-CycC was dependent on Med12-Med13. This observation also revealed that Cdk8-CycC and Med12-Med13 often have opposite transcriptional effects. Interestingly, Med12 and Med13 profiles overlapped significantly with that of the GATA factor Serpent. Accordingly, mutational analyses indicated that GATA sites are required for Med12-Med13 regulation of Serpent-dependent genes. Med12 and Med13 were also found to be required for Serpent-activated innate immunity genes in defense to bacterial infection. The results reveal a novel role for the Cdk8 module in Serpent-dependent transcription and innate immunity.
From the Institute of Biotechnology, University of Helsinki, P. O. Box 56, 00014 Helsinki.
Emilia
E
Kuuluvainen
From the Institute of Biotechnology, University of Helsinki, P. O. Box 56, 00014 Helsinki.
Heini
H
Hakala
From the Institute of Biotechnology, University of Helsinki, P. O. Box 56, 00014 Helsinki, the Department of Biosciences, University of Helsinki, P. O. Box 65, 00014 Helsinki.
Essi
E
Havula
From the Institute of Biotechnology, University of Helsinki, P. O. Box 56, 00014 Helsinki.
Michelle
M
Sahal Estimé
the Institute of Biomedical Technology, and BioMediTech, University of Tampere, 33014 Tampere, the Department of Pediatrics, Tampere University Hospital, 22521 Tampere, the Department of Pediatrics, Institute of Clinical Medicine, and Medical Research Center Oulu, University of Oulu, 90014 Oulu, and the Department of Children and Adolescents, Oulu University Hospital, 90029 Oulu, Finland.
Mika
M
Rämet
From the Institute of Biotechnology, University of Helsinki, P. O. Box 56, 00014 Helsinki, the Department of Biosciences, University of Helsinki, P. O. Box 65, 00014 Helsinki.
Ville
V
Hietakangas
From the Institute of Biotechnology, University of Helsinki, P. O. Box 56, 00014 Helsinki, tomi.makela@helsinki.fi.
Tomi P
TP
Mäkelä
D000818:Animals; D056850:Cyclin-Dependent Kinase 8 / Q000235:genetics*; D004330:Drosophila; D020869:Gene Expression Profiling; D007113:Immunity, Innate / Q000235:genetics*; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D014158:Transcription, Genetic
D056850:Cyclin-Dependent Kinase 8
Cdk8; Cyclin C; Drosophila; GATA Transcription Factor; Innate Immunity; Med12; Med13; Microarray; Serpent; Transcription