Aspergillus flavus, along with its notorious secondary metabolite aflatoxin B1 (AFB1), serious endangers human health. We previous revealed that histone methyltransferase complex COMPASS plays a crucial role in regulating various biological processes of A. flavus, but underlying mechanism is unclear. Here, through genetic assay and invading experiments, we found that Bre2, key subunit of COMPASS, regulates AFB1 bio-synthesis, fungal morphogenesis and virulence to crop and animal through H3K4 methylation. ChIP-seq and biochemistry analysis revealed that chromatin remolding factor (CRF) Arp9 is directly targeted by Bre2, and Arp9 implements bio-function through interacting with CRFs: RSC8, Arp7 and Sth1. ATAC analysis revealed that Arp9 deeply participates in fungal pathogenicity through regulating a serial secondary metabolism, morphogenesis and virulence associated regulators by modulating the chromatin conformation. The study revealed an epigenetic signaling pathway from COMPASS to Arp9 mediating chromatin remolding, which provides potential strategy for prevention and control of pathogenic fungi and mycotoxins.