On May 6, 2021, Yanhui Xu's group from IBS published a research article in Science entitled Structures of the human Mediator and Mediator-bound preinitiation complex, which  selected as the cover story formally  pressed at June 4,2021. This work provides the structure of the human Mediator at near-atomic resolution as well as the structure of the complete PIC-Mediator holocomplex. These structures provide insights into PIC-Mediator assembly and Mediator-stimulated CTD phosphorylation. TFIID may confer considerable complexity and dynamics of PIC-Mediator organization to accommodate highly dynamic processes of transcription initiation. The structures also provide a framework for further studies of Mediator-stimulated transcription activation by transcription factors.

As a critical transcription coactivator, the multisubunit Mediator complex binds RNA polymerase II (Pol II), facilitates preinitiation complex (PIC) assembly, and stimulates transcription and phosphorylation of the Pol II C-terminal domain (CTD). However, how these critical transcriptional events are coordinated by Mediator is not fully understood. Chen et al. determined the structures of human Mediator and Mediator-bound PIC in distinct conformational states, the latter of which represents a complete PIC-Mediator complex assembled on the 14-subunit transcription factor IID (TFIID). The structures show that Mediator undergoes reorganization during PIC-Mediator assembly, sandwiches and facilitates phosphorylation of Pol II CTD, and works with TFIID to organize TFIIH in PIC for transcription initiation.

COVER The human transcription preinnitition complex (PIC;pink and red) and multisubunit Meadiator complex (orange,left) are assembled into a supercomplex(76 polypeptides,molecular mass:4.1 megadaltons) on a promoter region of DNA (orange coil,center) to initiate gene transcription. Mediator binds RNA polymerase II (purple) in the PIC and stimulates phosphorylation of its C-terminal domain (highlighted in white), a critical event in transcription initiation. Illustration: V.Altounin/Science; Date:Y.Xu/Fudan University