GCN5 modulates salicylic acid homeostasis by regulating H3K14ac levels at the 5ʹ and 3ʹ ends of its target genes. GCN5 modulates salicylic acid homeostasis by regulating H3K14ac levels at the 5ʹ and 3ʹ ends of its target genes

The modification of histones by acetyl groups has a key role in the regulation of chromatin structure and transcription. The Arabidopsis thaliana histone acetyltransferase GCN5 regulates histone modifications as part of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) transcriptional coactivator complex. GCN5 was previously shown to acetylate lysine 14 of histone 3 (H3K14ac) in the promoter regions of its target genes; however, its binding did not systematically correlate with gene activation and the mechanism by which GCN5 controls transcription thus remained unclear. To gain insight into GCN5 function, we fine-mapped its genome-wide binding sites and explored the effect of GCN5 loss-of-function on the expression of its target genes, finding that GCN5 has a dual role in the regulation of H3K14ac levels in their 5ʹ and 3ʹ ends. We found that the gcn5 mutation leads to a genome-wide reduction of H3K14ac in the 5ʹ end of some of the GCN5 targets, a phenomenon associated to their down-regulated in the gcn5 mutant. By contrast, an increase of H3K14ac in the 3ʹ end was observed in GCN5 targets that are up-regulated in the gcn5 mutant, indicating that this protein plays a dual role in the control of H3K14ac levels and in the regulation of transcription. Furthermore, changes in H3K14ac levels in the gcn5 mutant correlated with changes in H3K9ac in a genome-wide fashion at both 5ʹ and 3ʹ ends, providing evidence for a molecular link between the deposition of these two histone modifications. Finally, we show that GCN5 participates in responses to biotic stress by repressing salicylic acid (SA) accumulation and SA-mediated immunity, highlighting the role of this protein in the regulation of the crosstalk between diverse developmental and stress-responsive physiological programs. Overall design: Examination of 1 histone modification (H3K14ac) in two allelic mutants of GCN5 and wild-type control and target analysis of GCN5-GFP protein (2 replicates)