Activator-Mediator binding regulates Mediator-cofactor interactions.

The 26-subunit, 1.2 MDa human Mediator complex is essential for expression of perhaps all protein-coding genes. Activator binding triggers major structural shifts within Mediator, suggesting a straightforward means to spatially and temporally regulate Mediator activity. By using mass spectrometry (MudPIT) and other techniques, we have compared the subunit composition of ...
Mediator in three different structural states: bound to the activator SREBP-1a, VP16, or an activator-free state. As expected, consensus Mediator subunits were similarly represented in each sample. However, we identify a set of cofactors that interact specifically with activator-bound but not activator-free Mediator, suggesting activator binding triggers new Mediator-cofactor interactions. Furthermore, MudPIT combined with biochemical assays reveals a nonoverlapping set of coregulatory factors associated with SREBP-Mediator vs. VP16-Mediator. These data define an expanded role for activators in regulating gene expression in humans and suggest that distinct, activator-induced structural shifts regulate Mediator function in gene-specific ways.
Mesh Terms:
Biochemistry, Cell Nucleus, Chromatin, Chromatography, Liquid, Cyclin-Dependent Kinase 8, Gene Expression Profiling, Gene Expression Regulation, Hela Cells, Herpes Simplex Virus Protein Vmw65, Humans, Mass Spectrometry, Mediator Complex, Models, Biological, Protein Binding, Sterol Regulatory Element Binding Protein 1
Proc. Natl. Acad. Sci. U.S.A.
Date: Jun. 22, 2010
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