ADA2 Forms Nuclear Condensates with GCN5 and ATP-Citrate Lyase (ACL) to Modulate H3K9 Acetylation at Genes...

SAGA (Spt-Ada-Gcn5 acetyltransferase) is a highly conserved histone acetyltransferase (HAT) complex in eukaryotes, playing a crucial role in regulating gene transcription during development. The complex consists of two core components: GCN5, the HAT subunit, and ADA2, which primarily functions as an adaptor and enhances the complex HAT activity. Beyond its well-established roles, it is discovered in this work that ADA2 in rice possesses a broadly existing intrinsically disordered region (IDR) that directs the formation of nuclear condensates. Moreover, ADA2 is found to interact with a subunit of ATP-citrate lyase (ACL), an enzyme that produces acetyl-CoA, leading to the formation of a GCN5-ADA2-ACL (GAA) complex. ADA2 promotes the condensation of both GCN5 and ACL in vivo. Within these condensates, ACL contributes to the production and enrichment of acetyl-CoA, thereby promoting histone acetylation. Genetic evidence showed that knock-out or suppression of these genes led to similarly diminished root meristem zone sizes and reduced branch primordia numbers, accompanied by significant reductions in genomic H3K9 acetylation and transcriptional attenuation of essential genes for meristem function. In summary, the findings unveil a novel mechanism of HAT action by forming phase separation to enrich acetyl-CoA within nuclear puncta, facilitating histone acetylation at target genes essential for meristem development.