Distinct roles for Mediator Cdk8 module subunits in Drosophila development.
Mediator (MED) is a conserved multisubunit complex bridging transcriptional activators and repressors to the general RNA polymerase II initiation machinery. In yeast, MED is organized in three core modules and a separable 'Cdk8 module' consisting of the cyclin-dependent kinase Cdk8, its partner CycC, Med12 and Med13. This regulatory module, specifically required for cellular adaptation to environmental cues, is thought to act through the Cdk8 kinase activity. Here we have investigated the functions of the four Cdk8 module subunits in the metazoan model Drosophila. Physical interactions detected among the four fly subunits provide support for a structurally conserved Cdk8 module. We analyzed the in vivo functions of this module using null mutants for Cdk8, CycC, Med12 and Med13. Each gene is required for the viability of the organism but not of the cell. Cdk8-CycC and Med12-Med13 act as pairs, which share some functions but also have distinct roles in developmental gene regulation. These data reveal functional attributes of the Cdk8 module, apart from its regulated kinase activity, that may contribute to the diversification of genetic programs.
Loncle
Nicolas
N
Centre de Biologie du Développement, UMR5544 du CNRS, Université Paul Sabatier, Toulouse Cedex 09, France.
Boube
Muriel
M
Joulia
Laurent
L
Boschiero
Claire
C
Werner
Michel
M
Cribbs
David L
DL
Bourbon
Henri-Marc
HM
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D056745:Cyclin C; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D046912:Multiprotein Complexes / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
C503678:CycC protein, Drosophila; D056745:Cyclin C; D016213:Cyclins; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; C498308:Cdk8 protein, Drosophila; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases