What do the structures of GCN5-containing complexes teach us about their function?

• Published in: Biochimica et biophysica acta. Gene regulatory mechanisms 2021-02, Vol.1864 (2), p.194614-194614, Article 194614
• Main Authors: Helmlinger, Dominique, Papai, Gábor, Devys, Didier, Tora, László
• Format: Article
• Language: English
• Subjects: Acetylation; ADA complex; ADA two A containing (ATAC) complex; Amino Acid Sequence - genetics; Animals; Arabidopsis - enzymology; Arabidopsis - genetics; Chromatin; Conserved Sequence; Cryoelectron Microscopy; Crystallography; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Evolution, Molecular; Gene Expression Regulation; Histone acetyl transferase; Histone deubiquitylase; Histones - metabolism; Humans; KAT2A; KAT2B; Life Sciences; Modular organization; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; Multienzyme Complexes - ultrastructure; p300-CBP Transcription Factors - genetics; p300-CBP Transcription Factors - metabolism; p300-CBP Transcription Factors - ultrastructure; Protein Structure, Quaternary - physiology; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; SAGA complex; Structure-Activity Relationship; Trans-Activators - genetics; Trans-Activators - metabolism; Trans-Activators - ultrastructure; Transcription
• ISSN: 1874-9399; 1876-4320
• DOI: 10.1016/j.bbagrm.2020.194614

Transcription initiation is a major regulatory step in eukaryotic gene expression. It involves the assembly of general transcription factors and RNA polymerase II into a functional pre-initiation complex at core promoters. The degree of chromatin compaction controls the accessibility of the transcription machinery to template DNA. Co-activators have critical roles in this process by actively regulating chromatin accessibility. Many transcriptional coactivators are multisubunit complexes, organized into distinct structural and functional modules and carrying multiple regulatory activities. The first nuclear histone acetyltransferase (HAT) characterized was General Control Non-derepressible 5 (Gcn5). Gcn5 was subsequently identified as a subunit of the HAT module of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex, which is an experimental paradigm for multifunctional co-activators. We know today that Gcn5 is the catalytic subunit of multiple distinct co-activator complexes with specific functions. In this review, we summarize recent advances in the structure of Gcn5-containing co-activator complexes, most notably SAGA, and discuss how these new structural insights contribute to better understand their functions. •Co-activators have critical roles in transcription by actively regulating chromatin accessibility.•Co-activators have modular organization.•The histone acetyl transferase (HAT) Gcn5/KAT2A is a subunit of several co-activator complexes.•The high-resolution structure of SAGA reveals new functional insights.•HAT modules of the different co-activator complexes may have different specificity and function.