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Structure of the human SAGA coactivator complex

Nogales, E.; Herbst, D.; Esbin, M.; Louder, R. K.; Dugast-Darzacq, C.; Dailey, G.; Fang, Q.; Darzacq, X.; Tjian, R.

2021-02-08 biophysics
10.1101/2021.02.08.430339 bioRxiv
Show abstract

Human SAGA is an essential co-activator complex that regulates gene expression by interacting with enhancer-bound activators, recruiting transcriptional machinery, and modifying chromatin near promoters. Subunit variations and the metazoan-specific requirement of SAGA in development hinted at unique structural features of the human complex. Our 2.9 [A] structure of human SAGA reveals intertwined functional modules flexibly connected to a core that distinctively integrates mammalian paralogs, incorporates U2 splicing subunits, and features a unique interface between the core and the activator-binding TRRAP. Our structure sheds light on unique roles and regulation of human coactivators with implications for transcription and splicing that have relevance in genetic diseases and cancer.

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