The Mediator of RNA polymerase II

Abstract

Mediator (TRAP/ARC/PC2) is a large (22-28 subunit) protein complex that binds RNA polymerase II and controls transcription from class II genes. The evolutionarily conserved core of Mediator is found in all eukaryotes. It binds RNA polymerase II and is probably critical for basal transcription but it also mediates activation and repression of transcription. During evolution the complex has acquired additional species-specific subunits. These serve as an interface for regulatory factors and support specific signalling pathways. Recent mechanistic studies are consistent with the hypothesis that Mediator marks genes for binding by RNA polymerase II whereupon it subsequently activates the preinitiation complex. It is further likely that Mediator coordinates the recruitment of chromatin-modifying cofactor activities.

A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways inC. elegans

“…Although multiple Mediator subunits have been found to directly interact with NHRs (Blazek et al 2005), this is the first report describing an interaction of an NHR with MDT-15/MED15 proteins. NHRs commonly target coregulators via canonical LxxLL motifs.…”

“…The MDT-15 proteins exhibit sequence similarity to yeast MED15/ GAL11 (subsequently named GAL11) ) and human MED15/ARC105/TIG-1/PCQAP proteins (subsequently named MED15) ). GAL11 and MED15 proteins are subunits of the yeast and human Mediator complexes, respectively, multisubunit protein complexes that act as transcriptional coregulators for regulatory factors (Blazek et al 2005;Malik and Roeder 2005).…”

“…The C. elegans genome appears to lack PGC-1-related proteins (Knutti et al 2000); in addition, the conservation between mammalian MED1 and its C. elegans ortholog, MDT-1.1/SOP-3, is weak (Blazek et al 2005). Thus, we hypothesized that distinct C. elegans coregulators might confer physiological effects similar to those coordinated by PGC-1 and MED1.…”

The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220

“…The Mediator complex is the key coactivator for many transcription factors (reviewed in refs. [4][5][6][7][8]. The interaction of activators with Mediator stimulates preinitiation complex assembly on promoter DNA.…”

“…Substantial evidence argues that Mediator activates transcription, at least in part, by direct interactions with DNA-binding transcriptional activators bound at upstream promoter elements and enhancers with polII and one or more of the general initiation factors bound at the core promoter. Notably, different Mediator subunits are targets for interactions with the transcriptional activation domains of different DNA-binding transcriptional activators (4,7,9). As a consequence, it is of great interest to identify subunits that serve as contact sites for the large collection of DNA-binding transcriptional activators.…”