Transcriptional regulation and mediator

Eukaryotic transcription regulation relies on co-activator complexes such as the SAGA or Mediator complexes. The Mediator is required for the regulation of mRNA transcription by Pol II. The mechanism of how Mediator enables regulated transcription is unknown, mainly due to limited structure-function information. Mediator is very large, comprising 25 subunits in yeast, with a total molecular weight of one mega-Dalton. Mediators in higher eukaryotes are larger than they are in yeast, with 30 or more subunits making up the human version. One feature of the mammalian Mediator is that its subunit composition is variable, raising the possibility that there are several versions, each one responding to a different, although possibly overlapping set of activators. Our lab is studying the arrangement and organization of Mediator complex subunits to understand its possible architecture in higher eukaryotes. We are trying to decipher how different subunits contribute to the structural integrity of this complex. In particular, it is necessary to know how the higher eukaryote specific Mediator subunits, namely MED16, MED23, MED24, MED25 and MED26 interact with the core Mediator. We combine molecular, structural and cell biology in a multidisciplinary approach to elucidate the molecular bases of mammalian Mediator complex structural organization and assembly mechanism.


The human Med23 - Nat. Comm 2018
DOI: 10.1038/s41467-018-05967-y