The KdmB-EcoA-RpdA-SntB chromatin complex binds regulatory genes and coordinates fungal development with mycotoxin synthesis

Abstract

Chromatin complexes control a vast number of epigenetic developmental processes. Filamentous fungi present an important clade of microbes with poor understanding of underlying epigenetic mechanisms. Here, we describe a chromatin binding complex in the fungus Aspergillus nidulans composing of a H3K4 histone demethylase KdmB, a cohesin acetyltransferase (EcoA), a histone deacetylase (RpdA) and a histone reader/E3 ligase protein (SntB). In vitro and in vivo evidence demonstrate that this KERS complex is assembled from the EcoA-KdmB and SntB-RpdA heterodimers. KdmB and SntB play opposing roles in regulating the cellular levels and stability of EcoA, as KdmB prevents SntB-mediated degradation of EcoA. The KERS complex is recruited to transcription initiation start sites at active core promoters exerting promoter-specific transcriptional effects. Interestingly, deletion of any one of the KERS subunits results in a common negative effect on morphogenesis and production of secondary metabolites, molecules important for niche securement in filamentous fungi. Consequently, the entire mycotoxin sterigmatocystin gene cluster is downregulated and asexual development is reduced in the four KERS mutants. The elucidation of the recruitment of epigenetic regulators to chromatin via the KERS complex provides the first mechanistic, chromatin-based understanding of how development is connected with small molecule synthesis in fungi.

F-box receptor mediated control of substrate stability and subcellular location organizes cellular development of Aspergillus nidulans

“…Endogenously expressed SkpA-GFP in its native locus was predominantly localized in the nucleus, whereas less endogenously expressed CulA-GFP was present there ( Fig 1A ). In several previous studies, we had shown that SkpA was expressed equally throughout all developmental stages [ 45 , 46 ]. Using SkpA-GFP fusion, SkpA interactors were identified by GFP pull-downs and mass spectrometry (MS) during vegetative growth, osmotic and oxidative stress, and asexual or sexual development ( Fig 1B , S1 – S7 Tables and Table A in S9 Table ).…”

SntB triggers the antioxidant pathways to regulate development and aflatoxin biosynthesis inAspergillus flavus

“…SntB was reported as an important epigenetic reader. In A. flavus , SntB was reported to regulate global histone modifications (acetylation and methylation) and interact with EcoA and RpdA to form a conserved chromatin regulatory complex [20, 29]. Loss of sntB in Magnaporthe orzyae also led to an increase in H3 acetylation [48].…”

“…In Penicillium expansum , SntB regulated the development, patulin and citrinin production, and virulence on apples [28]. In A. nidulans , SntB combined with a H3K4 histone demethylase KdmB, a cohesin acetyltransferase (EcoA), and a histone deacetylase (RpdA) to form a chromatin binding complex and bound to regulatory genes and coordinated fungal development with mycotoxin synthesis [29]. sntB also regulated the virulence in Fusarium oxysporum , and respiration in F. oxysporum and Neurospora crassa [30, 31].…”

Genetic Regulation of Mycotoxin Biosynthesis

“…Deletion of the epigenetic reader gene sntB in A. nidulans and A. flavus changed the global levels of histone H3K9K14 acetylation, leading to the inhibition of ST and AF ( Figure 2 ) [ 41 , 134 ], but induction of a silent secondary metabolite aspergillicin [ 135 ]. Most recently, it has been shown that SntB is part of a newly discovered chromatin binding complex known as the KERS complex, which like the Velvet complex, also links development to secondary metabolism [ 136 ]. Deletion of the histone acetyltransferase gene rtt109 significantly decreased the production of AFs in A. flavus [ 42 ].…”