Project AP01
Structures of extended PIC-Mediator complexes and mechanisms of transcription regulation
About
The Mediator complex is a general coactivator of RNA polymerase II (Pol II) transcription that forms a bridge between regulatory transcription factors (TFs) and gene promoters. Over the last two decades, we provided structures of the conserved core of yeast Mediator and the core Mediator in complex with the Pol II pre-initiation complex (PIC). We also obtained structures of a 20-subunit human core Mediator in complex with the PIC. We now propose to extend our structural work to the complete human Mediator and to complexes of the PIC-Mediator assembly with the +1 nucleosome and regulatory TFs. Our long-term goal is to provide the mechanistic basis for Mediator-dependent human gene regulation.