# COMPASS subunit Bre2 regulates chromatin remodeler Arp9 to control Aspergillus flavus aflatoxin synthesis and virulence

**Authors:** Zhenhong Zhuang, Minghui Sun, Dandan Wu, Dongmei Ma, Lin Chen, Xiaohua Pan, Hong Lin, Yu Li, Xuezhen Ma, Shihua Wang

PMC · DOI: 10.1038/s41467-026-69877-0 · 2026-02-20

## TL;DR

This study reveals how a key protein in a histone methyltransferase complex regulates aflatoxin production and fungal virulence in Aspergillus flavus.

## Contribution

The novel finding is that Bre2 regulates the chromatin remodeler Arp9, linking H3K4 methylation to aflatoxin biosynthesis and pathogenicity.

## Key findings

- Bre2 modulates H3K4 methylation to regulate aflatoxin biosynthesis and fungal virulence.
- Arp9 interacts with other chromatin remodeling factors to influence fungal pathogenicity.
- Arp9 modulates chromatin conformation of genes involved in secondary metabolism and virulence.

## Abstract

Aspergillus flavus, along with its notorious secondary metabolite aflatoxin B1 (AFB1), seriously endangers human health. Histone methyltransferase complex COMPASS (complex of proteins associated with Set1) plays a crucial role in regulating aflatoxin biosynthesis and virulence of A. flavus, but the underlying mechanism is unclear. Here, we find that Bre2, the key subunit of COMPASS, regulates AFB1 biosynthesis, fungal morphogenesis, and virulence through modulation of H3K4 methylation. ChIP-seq and biochemical analyses reveal that chromatin remodeling factor (CRF) Arp9 is directly targeted by Bre2, and Arp9 exerts bio-functions through interacting with the other CRFs such as RSC8, Arp7, and Sth1. ATAC-seq results indicate that Arp9 contributes to fungal pathogenicity by modulating chromatin conformation of genes that are involved in secondary metabolism, morphogenesis, and virulence. The study reveals an epigenetic signaling pathway mediated by chromatin remodeler Arp9 and provides a potential strategy for the control of pathogenic fungi and mycotoxins.

Aspergillus flavus, producing carcinogenic aflatoxin B₁ (AFB₁), contaminates crops and invades animals. The authors identify Bre2, a key COMPASS histone methyltransferase subunit, regulates AFB₁ biosynthesis and fungal pathogenesis, providing insight into potential A. flavus and AFB₁ control strategies.

## Linked entities

- **Genes:** ASH2L (ASH2 like, histone lysine methyltransferase complex subunit) [NCBI Gene 9070], APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic subunit 3G) [NCBI Gene 60489], SMARCC1 (SWI/SNF related BAF chromatin remodeling complex subunit C1) [NCBI Gene 6599], ARP7 (actin-related protein 7) [NCBI Gene 825254], sth-1 (SpermaTHecal expression) [NCBI Gene 179188]
- **Proteins:** ASH2L (ASH2 like, histone lysine methyltransferase complex subunit), APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic subunit 3G), SMARCC1 (SWI/SNF related BAF chromatin remodeling complex subunit C1), ARP7 (actin-related protein 7), sth-1 (SpermaTHecal expression)
- **Chemicals:** aflatoxin B1 (PubChem CID 186907)
- **Species:** Aspergillus flavus (taxon 5059)

## Full-text entities

- **Genes:** aflK (aflK/ vbs/ VERB synthase) [NCBI Gene 64848023] {aka G4B84_005791, vbs}, aflP (aflP/ omtA/ omt-1/ O-methyltransferase A) [NCBI Gene 64848025] {aka G4B84_005793, omt-1, omtA}, aflS (aflS/ pathway regulator) [NCBI Gene 64848035] {aka G4B84_005803}, aflQ (O-methylsterigmatocystin oxidoreductase) [NCBI Gene 64848024] {aka G4B84_005792, ord-1, ordA}, brlA [NCBI Gene 64843361], aflC (beta-ketoacyl synthase) [NCBI Gene 64848041] {aka G4B84_005809, pksA, pksL1}, aflD [NCBI Gene 64848039]
- **Diseases:** CLD (MESH:D008107), dysplasia (MESH:D015792), ND (MESH:C537849), carcinogenesis (MESH:D063646), infection (MESH:D007239), WT (MESH:D009396), fungal (MESH:D009181), HCC (MESH:D006528), ulcerative colitis (MESH:D003093)
- **Chemicals:** methanol (MESH:D000432), AFB1 (MESH:D016604), NaCl (MESH:D012965), MgCl2 (MESH:D015636), Uridine (MESH:D014529), acid (MESH:D000143), polyethylene glycol (MESH:D011092), EDTA (MESH:D004492), nitrogen (MESH:D009584), Ile (MESH:D007532), K2HPO4 (MESH:C013216), dichloromethane (MESH:D008752), NP-40 (MESH:C010615), uracil (MESH:D014498), cefiderocol (MESH:C000612166), acetonitrile (MESH:C032159), azoles (MESH:D001393), ammonium tartrate (MESH:C029768), chitin (MESH:D002686), agar (MESH:D000362), NaNO3 (MESH:C031618), water (MESH:D014867), phenol (MESH:D019800), TRIzol (MESH:C411644), AFs (MESH:D000348), terpenoids (MESH:D013729), staurosporine (MESH:D019311), SDS (MESH:D012967), CaCl2 (MESH:D002122), DTT (MESH:D004229), ethanol (MESH:D000431), polyketide (MESH:D061065), Asn (MESH:D001216), maltose (MESH:D008320), CM (-), 5-FOA (MESH:C001242), MgSO4 (MESH:D008278), peroxide (MESH:D010545), emodin (MESH:D004642), carbohydrate (MESH:D002241), Phe (MESH:D010649), D-mannitol (MESH:D008353), fluconazole (MESH:D015725), chloroform (MESH:D002725), sucrose (MESH:D013395), lipid (MESH:D008055), KCl (MESH:D011189), lysine (MESH:D008239), Tween-20 (MESH:D011136), beta-glucan (MESH:D047071), momilactone B (MESH:C477203), glucose (MESH:D005947), DMSO (MESH:D004121)
- **Species:** Candida albicans (species) [taxon 5476], Pyricularia grisea (species) [taxon 148305], Aspergillus fumigatus (species) [taxon 746128], Mus musculus (house mouse, species) [taxon 10090], Verticillium dahliae (species) [taxon 27337], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Fusarium graminearum (species) [taxon 5518], Aspergillus piperis (species) [taxon 319630], Komagataella pastoris (species) [taxon 4922], Serendipita indica (species) [taxon 65672], Cryptococcus neoformans (Cryptococcus neoformans serotype A, species) [taxon 5207], Parastagonospora nodorum (species) [taxon 13684], Arachis hypogaea (goober, species) [taxon 3818], Hepatitis B virus (no rank) [taxon 10407], Aspergillus bombycis (species) [taxon 109264], Aspergillus glaucus (species) [taxon 41413], Galleria mellonella (greater wax moth, species) [taxon 7137], A. flavus [taxon 315677], Aspergillus nomiae (species) [taxon 41061], Penicillium oxalicum (species) [taxon 69781], Aspergillus flavus (species) [taxon 5059], Aspergillus clavatus (species) [taxon 5057], Homo sapiens (human, species) [taxon 9606], Aspergillus phoenicis (species) [taxon 5063], Aspergillus violaceofuscus (species) [taxon 657443], Aspergillus bertholletiae (species) [taxon 1226010], Aspergillus tamarii (species) [taxon 41984], Zymoseptoria tritici (species) [taxon 1047171], Acinetobacter baumannii (species) [taxon 470], Bombyx mori (domestic silkworm, species) [taxon 7091], Aspergillus steynii (species) [taxon 306088], Drosophila melanogaster (fruit fly, species) [taxon 7227]
- **Cell lines:** Com-Bre2 — Mus musculus (Mouse), Hybridoma (CVCL_XB10)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12923686/full.md

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Source: https://tomesphere.com/paper/PMC12923686