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

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 coactivators. 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.

Automated summary

Transcription initiation plays a crucial role in regulating gene expression in eukaryotes, involving the assembly of transcription factors and RNA polymerase II into a pre-initiation complex. Chromatin compaction determines the accessibility of the transcription machinery to DNA, with co-activators actively regulating chromatin accessibility. Co-activators like Gcn5 are part of multifunctional complexes with distinct functions, contributing to a better understanding of their structural and functional roles.