GCN5-ADA2 Recruits ATP-Citrate Lyase (ACL) and Forms Condensates to Modulate Acetylation at H3K9 for Functional Genes in Rice Meristem

The SAGA complex is a highly conserved histone acetyltransferase (HAT) complex in eukaryotes, playing crucial role in regulating gene transcription throughout organismal development. The complex consists of two core components: GCN5, the HAT subunit, and ADA2, which primarily functions as an adaptor, facilitating interactions between GCN5 and other proteins and enhancing the complex’s accessibility to nucleosomes. Beyond its well-established roles, we discovered that, in rice, ADA2 possesses an evolutionary conserved intrinsically disordered region (IDR) that directs the SAGA complex to form nuclear condensates. Moreover, we identified a physical interaction between ADA2 and ATP-citrate lyase subunit A2 (ACLA2), leading to the formation of a GCN5-ADA2-ACLA2 (GAA) complex. Both GCN5 and ACLA2 exhibit phase separation in vivo, a process that is dependent on ADA2. 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 the three indicated genes collectively resulted in diminished meristem zones at both root tips and inflorescences, accompanied by a significant reduction in genomic H3K9 acetylation and transcriptional attenuation of essential genes for meristem function. In summary, our findings unveiled a novel mechanism for HAT in modulating gene transcription and plant development, in which the GAA complex phase separates and enriches acetyl-CoA metabolites within the nuclear puncta to facilitate the acetylation of histones at target genes. Transcriptome detection by RNA-seq for rice root tips and inflorescence meristems in wild type and the three indicated mutants/RNAi backgrounds. Genomic binding detection for the three components of GAA complex via CUT&Tag. Genomic histone H3 K9 acetylation detection of root tips for wild type and the three indicated mutants/RNAi backgrounds.