GCN5

GCN5, short for General Control Non-derepressing 5, is a histone acetyltransferase (HAT) enzyme in eukaryotes. It is a core component of the SAGA (Spt-Ada-Gcn5 acetyltransferase) transcriptional coactivator complex and is responsible for acetylation of histone H3 lysines, particularly H3K9 and H3K14, although substrate specificity can vary by organism and context. Through histone acetylation, GCN5 promotes an open chromatin state and facilitates transcription initiation and elongation. GCN5 uses acetyl-CoA as a donor of acetyl groups.

Genetic and functional context: In Saccharomyces cerevisiae, GCN5 is one of the key coactivators for several transcriptional programs and is named for its role in general control of transcription; in mammals, the GCN5 gene is typically called KAT2A, with a paralog KAT2B (PCAF). The two mammalian HATs share substantial sequence similarity and overlapping functions but can have unique regulatory roles and target gene sets. In SAGA, GCN5 forms the HAT module with ADA2, ADA3, and SGF29, and cooperates with other modules including a deubiquitinase module and TBP-binding components.

Biological significance: GCN5 activity influences development, cell cycle control, stress responses, and metabolism. It is recruited to chromatin by transcription factors and promoter-bound activators, and its activity can be regulated by complex assembly, post-translational modifications, and interaction with other chromatin modifiers. Dysregulation of GCN5 and related HAT activity has been linked to human diseases, including cancer, and is a subject of ongoing research in epigenetics and transcriptional regulation.