Research Article

Structural insights into preinitiation complex assembly on core promoters

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Science  01 Apr 2021:
eaba8490
DOI: 10.1126/science.aba8490

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Abstract

Transcription factor IID (TFIID) recognizes core promoters and supports preinitiation complex (PIC) assembly for RNA polymerase (Pol) II-mediated eukaryotic transcription. Here, we determined the structures of human TFIID-based PIC in three stepwise assembly states and revealed two-track PIC assembly: stepwise promoter deposition to Pol II and extensive modular reorganization on track I (on TATA-DBE promoters) versus direct promoter deposition on track II (on TATA-only and TATA-less promoters). The two tracks converge at ~50-subunit holo-PIC in identical conformation, whereby TFIID stabilizes PIC organization and supports loading (CDK)-activating kinase (CAK) onto Pol II and CAK-mediated phosphorylation of Pol II C-terminal domain. Unexpectedly, TBP of TFIID similarly bends TATA box and TATA-less promoters in PIC. Our study provides structural visualization of stepwise PIC assembly on highly diversified promoters.

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