Architecture of the Saccharomyces cerevisiae NuA4/TIP60 complex
TL;DR: These structures elucidate the detailed architecture and molecular interactions between NuA4 subunits and offer exciting insights into the scaffolding and regulatory mechanisms of Tra1 pseudokinase.
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Abstract: The NuA4/TIP60 acetyltransferase complex is required for gene regulation, DNA repair and cell cycle progression. The limited structural information impeded understanding of NuA4/TIP60 assembly and regulatory mechanism. Here, we report the 4.7 A cryo-electron microscopy (cryo-EM) structure of a NuA4/TIP60 TEEAA assembly (Tra1, Eaf1, Eaf5, actin and Arp4) and the 7.6 A cryo-EM structure of a TEEAA-piccolo assembly (Esa1, Epl1, Yng2 and Eaf6). The Tra1 and Eaf1 constitute the assembly scaffold. The Eaf1 SANT domain tightly binds to the LBE and FATC domains of Tra1 by ionic interactions. The actin/Arp4 peripherally associates with Eaf1 HSA domain. The Eaf5/7/3 (TINTIN) and piccolo modules largely pack against the FAT and HEAT repeats of Tra1 and their association depends on Eaf1 N-terminal and HSA regions, respectively. These structures elucidate the detailed architecture and molecular interactions between NuA4 subunits and offer exciting insights into the scaffolding and regulatory mechanisms of Tra1 pseudokinase.
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Citations
Depletion of TRRAP Induces p53-Independent Senescence in Liver Cancer by Down-Regulating Mitotic Genes.
Suet-Yan Kwan,Ankur Sheel,Chun-Qing Song,Xiao-Ou Zhang,Tingting Jiang,Hien Dang,Yueying Cao,Deniz M. Ozata,Haiwei Mou,Hao Yin,Zhiping Weng,Zhiping Weng,Xin Wei Wang,Wen Xue +13 more
TL;DR: It is shown that depletion of TRRAP or its co‐factor, histone acetyltransferase KAT5, inhibits HCC cell growth through induction of p53‐independent and p21‐independent senescence and Targeting the TRR AP/KAT5 complex is a potential therapeutic strategy for HCC.
64
Arabidopsis YAF9 histone readers modulate flowering time through NuA4-complex-dependent H4 and H2A.Z histone acetylation at FLC chromatin.
Pedro Crevillén,Ángeles Gómez-Zambrano,Juan Antonio López,Jesús Vázquez,Manuel Piñeiro,Jose A. Jarillo +5 more
TL;DR: The work highlights the key role exerted by YAF9 homologues in the posttranslational modification of canonical histones and variants that regulate gene expression in plants to control development and shows that YAF 9A binds FLC chromatin and that Yaf9 proteins regulate FLC expression by modulating the acetylation levels of H2A.Z.
51
Structure of the human SAGA coactivator complex.
Dominik A Herbst,Dominik A Herbst,Meagan N. Esbin,Robert K. Louder,Robert K. Louder,Claire Dugast-Darzacq,Gina M. Dailey,Qianglin Fang,Qianglin Fang,Qianglin Fang,Xavier Darzacq,Robert Tjian,Eva Nogales +12 more
TL;DR: In this paper, the structure of human SAGA (hSAGA) has been analyzed in the presence of an inositol hexakisphosphate (InsP6) binding site in TRRAP.
44
Insights Into the Function of the NuA4 Complex in Plants.
Loreto Espinosa-Cores,Laura Bouza-Morcillo,Javier Barrero-Gil,Verónica Jiménez-Suárez,Ana Lázaro,Raquel Piqueras,Jose A. Jarillo,Manuel Piñeiro +7 more
TL;DR: A review of the current state of knowledge on plant putative NuA4 subunits and discuss the latest progress concerning the function of this chromatin modifying complex is presented in this article.
Dynamic modules of the coactivator SAGA in eukaryotic transcription
TL;DR: A protein that helps add epigenetic information to genome, SAGA, controls many aspects of gene activation, potentially making it a target for cancer therapies and disease implications for fine-tuning gene expression are illustrated.
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