GCN5 modulates salicylic acid homeostasis by regulating H3K14ac levels at the 5' and 3' 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 5' and 3' ends. We found that the gcn5 mutation leads to a genome-wide reduction of H3K14ac in the 5' 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 3' 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 5' and 3' 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)