Transcription elongation regulated by H2B deubiquitination and H2A.Z eviction enables fungal virulence

The regulation of RNA polymerase II (Pol II) pausing and its subsequent release during transcription elongation is crucial for pathogenic fungi to reprogram gene expression and establish successful infection. However, the mechanisms underlying Pol II regulation in these organisms remain underexplored. Combining with biochemical assays, ChIP-seq method, and biological analyses, we demonstrate that H2B deubiquitination (H2Bdeub1) and the eviction of histone variant H2A.Z jointly regulate Pol II pause release in Fusarium graminearum. Upon infection, deubiquitinase FgUbp8 recruits the Inositol Requiring 80 Complex (INO80-C) to remove H2A.Z from +1 nucleosomes, relaxing the chromatin structure and enabling the kinases FgCtk1 and FgBur1 to phosphorylate the C-terminal domain of Pol II and the elongation factor FgSpt5, respectively. These events promote the release of paused Pol II and activate the transcription of pathogenesis-related genes. Our findings uncover a novel regulatory mechanism wherein H2Bdeub1 and H2A.Z removal coordinate Pol II pause release, offering significant insights into transcription elongation regulation in eukaryotes and advancing the understanding of fungal gene regulation during infection.