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Published on: January 22, 2019
Activator-Mediator binding regulates Mediator-cofactor interactions
Christopher C Ebmeier1, Dylan J Taatjes
1Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
Summary
Human Mediator complex structure changes upon activator binding, revealing new cofactor interactions. This suggests activators fine-tune gene expression by altering Mediator function in specific ways.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- The human Mediator complex, a 26-subunit assembly, is crucial for regulating the expression of protein-coding genes.
- Activator proteins binding to Mediator induce significant structural changes, implying a mechanism for controlling Mediator activity.
- Understanding these structural dynamics is key to deciphering gene expression control.
Purpose of the Study:
- To investigate the subunit composition of the human Mediator complex in different structural states.
- To identify cofactors that interact with Mediator upon activator binding.
- To compare Mediator-cofactor interactions when bound to distinct activators (SREBP-1a and VP16).
Main Methods:
- Multi-dimensional protein identification technology (MudPIT) mass spectrometry.
- Biochemical assays.
- Comparative analysis of Mediator complex composition across activator-bound and activator-free states.
Main Results:
- Consensus Mediator subunits were consistently found across all tested states.
- A distinct set of cofactors were identified that bind specifically to activator-bound Mediator, not the free form.
- Non-overlapping coregulatory factors were associated with SREBP-Mediator and VP16-Mediator complexes.
Conclusions:
- Activator binding to the Mediator complex induces new cofactor interactions.
- Distinct activators recruit unique sets of coregulatory factors.
- These findings highlight an expanded role for activators in human gene regulation, with activator-induced structural changes mediating gene-specific control of Mediator function.
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