Journal Article

Structure of SAGA and mechanism of TBP deposition on gene promoters

Papai, Gabor, Ben-Shem, Adam, Frechard, Alexandre, Schultz, Patrick, Kolesnikova, Olga, Crucifix, Corinne

2020

Overview

SAGA (Spt–Ada–Gcn5–acetyltransferase) is a 19-subunit complex that stimulates transcription via two chromatin-modifying enzymatic modules and by delivering the TATA box binding protein (TBP) to nucleate the pre-initiation complex on DNA, a pivotal event in the expression of protein-encoding genes 1 . Here we present the structure of yeast SAGA with bound TBP. The core of the complex is resolved at 3.5 Å resolution (0.143 Fourier shell correlation). The structure reveals the intricate network of interactions that coordinate the different functional domains of SAGA and resolves an octamer of histone-fold domains at the core of SAGA. This deformed octamer deviates considerably from the symmetrical analogue in the nucleosome and is precisely tuned to establish a peripheral site for TBP, where steric hindrance represses binding of spurious DNA. Complementary biochemical analysis points to a mechanism for TBP delivery and release from SAGA that requires transcription factor IIA and whose efficiency correlates with the affinity of DNA to TBP. We provide the foundations for understanding the specific delivery of TBP to gene promoters and the multiple roles of SAGA in regulating gene expression. Structural studies on the yeast transcription coactivator complex SAGA (Spt–Ada–Gcn5–acetyltransferase) provide insights into the mechanism of initiation of regulated transcription by this multiprotein complex, which is conserved among eukaryotes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 101/28 / 631/337/572 / 631/535/1258/1259 / 82/83 / Acetyltransferase / Binding proteins / Binding Sites / Biochemical analysis / Biochemistry, Molecular Biology / Chromatin / Deoxyribonucleic acid / DNA / DNA, Fungal - chemistry / DNA, Fungal - metabolism / Domains / Fungal Proteins - chemistry / Fungal Proteins - metabolism / Gene expression / Gene Expression Regulation, Fungal / Genes / Genetic aspects / Genomics / Histone Acetyltransferases - chemistry / Histone Acetyltransferases - metabolism / Histones - chemistry / Histones - metabolism / Humanities and Social Sciences / Initiation complex / Life Sciences / Microscopy / Models, Molecular / multidisciplinary / Pichia - chemistry / Pichia - genetics / Promoter Regions, Genetic - genetics / Promoters / Promoters (Genetics) / Protein Binding / Protein Conformation / Proteins / RNA polymerase / Saccharomyces cerevisiae - chemistry / Saccharomyces cerevisiae Proteins - chemistry / Saccharomyces cerevisiae Proteins - metabolism / Science / Science (multidisciplinary) / Steric hindrance / Structural Biology / Structure / Tata box / TATA-Binding Protein Associated Factors - chemistry / TATA-Binding Protein Associated Factors - metabolism / TATA-Box Binding Protein - chemistry / TATA-Box Binding Protein - metabolism / Trans-Activators - chemistry / Trans-Activators - metabolism / Transcription Factor TFIIA - chemistry / Transcription Factor TFIIA - metabolism / Transcription Factor TFIID - chemistry / Transcription Factor TFIID - metabolism / Transcription factors / Yeast