Inhibition of histone acetyltransferase GCN5 by a transcription factor FgPacC controls fungal adaption to host-derived iron stress

Fg infection induces host alkalinization, and the pH-dependent transcription factor FgPacC undergoes a proteolytic cleavage into the functional isoform named FgPacC30 under alkaline host environment. Subsequently FgPacC30 binds to a GCCAR(R=A/G)G element at the promoters of the genes involved in iron uptake and inhibits their expression, leading to adaption of Fg to high-iron stress. Mechanistically, FgPacC30 binds to FgGcn5 protein, a catalytic subunit of Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex, leading to deregulation of histone acetylation at H3K18 and H2BK11, and repression of iron uptake genes. It was proved by RNA-seq and ChIP-seq data that the transcription factor FgPacC affects the expression of iron uptake genes by mediating the deregulation of histone acetylation at H3K18 and H2BK11

Fg感染可诱导宿主发生碱化，在碱性宿主环境中，pH依赖性转录因子FgPacC会经蛋白水解切割形成功能型同工型FgPacC30。随后，FgPacC30结合至铁吸收相关基因启动子区域的GCCAR(R=A/G)G基序，抑制这些基因的表达，使Fg能够适应高铁胁迫。从分子机制层面来看，FgPacC30可结合Spt-Ada-Gcn5乙酰转移酶（Spt-Ada-Gcn5 Acetyltransferase, SAGA）复合物的催化亚基FgGcn5蛋白，导致H3K18与H2BK11位点的组蛋白乙酰化失衡，进而抑制铁吸收基因的转录。研究人员通过RNA测序（RNA-seq）与染色质免疫沉淀测序（ChIP-seq）数据证实，转录因子FgPacC可通过介导H3K18和H2BK11位点的组蛋白乙酰化失衡，调控铁吸收基因的表达。