Structural basis of a SWI/SNF-associated transcription pre-initiation complex.

Nagai, Shigeki; Yang, Chun; Chen, Dong-Hua; Trnka, Michael J; Bushnell, David A; Burlingame, Alma L; Murakami, Kenji; Kornberg, Roger D · Cell · 2026

basic_science · Level V

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Abstract

The mating type switching/sucrose non-fermenting (SWI/SNF) chromatin remodeling complex removes and repositions nucleosomes at promoters for the initiation of transcription. Though long thought to function independently, we find that SWI/SNF is an integral component of the transcription machinery. SWI/SNF associates with an RNA polymerase II pre-initiation complex (PIC), Mediator, and a nucleosome, and the entire assembly dimerizes to form a giant 7-megadalton complex. We present high-resolution cryo-electron microscopy (cryo-EM) structures of both PIC-Mediator-SWI/SNF and PIC-Mediator-SWI/SNF-nucleosome complexes, together with results of cross-linking and mass spectrometry. The structures reveal how SWI/SNF enhances the initiation of transcription through stabilization of PIC organization and concerted remodeling of the so-called +1 nucleosome. The structural model suggests the coordinated actions of two DNA translocases, Snf2 of SWI/SNF and Ssl2 of TFIIH, for the initiation of transcription.