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Publication Abstract from PubMed

The 1.3-megadalton transcription factor IID (TFIID) is required for preinitiation complex (PIC) assembly and RNA polymerase II (Pol II)-mediated transcription initiation on almost all genes. The 26-subunit Mediator stimulates transcription and cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of the Pol II C-terminal domain (CTD). We determined the structures of human Mediator in the Tail module-extended (at near-atomic resolution) and Tail-bent conformations and structures of TFIID-based PIC-Mediator (76 polypeptides, ~4.1 megadaltons) in four distinct conformations. PIC-Mediator assembly induces concerted reorganization (Head-tilting and Middle-down) of Mediator and creates a Head-Middle sandwich, which stabilizes two CTD segments and brings CTD to CDK7 for phosphorylation; this suggests a CTD-gating mechanism favorable for phosphorylation. The TFIID-based PIC architecture modulates Mediator organization and TFIIH stabilization, underscoring the importance of TFIID in orchestrating PIC-Mediator assembly.

Structures of the human Mediator and Mediator-bound preinitiation complex.,Chen X, Yin X, Li J, Wu Z, Qi Y, Wang X, Liu W, Xu Y Science. 2021 Jun 4;372(6546):eabg0635. doi: 10.1126/science.abg0635. Epub 2021 , May 6. PMID:33958484^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.