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Journal of Integrative Agriculture  2025, Vol. 24 Issue (8): 3087-3094    DOI: 10.1016/j.jia.2024.01.006
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A missense mutation in the Sin3 subunit of Rpd3 histone deacetylase complex bypasses the requirement for FNG1 in wheat scab fungus

Huaijian Xu1, Ruoxuan Jiang1, Xianhui Fu1, Qinhu Wang1, Yutong Shi1, Xiaofei Zhao1, Cong Jiang1#, Hang Jiang2#

1 State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, College of Plant Protection, Northwest A&F University, Yangling 712100, China

2 Shandong Key Laboratory for Green Prevention and Control of Agricultural Pests, Institute of Plant Protection, Shandong Academy of Agricultural Sciences, Jinan 250100, China

 Highlights 
A glutamate residue (E810) in FgSin3 is important for its biological functions.
Our findings provide key experimental evidence supporting the structural model of the RPD3 complex.
The highly conserved E810, along with its variable neighboring residues, represents a potential target for developing disease control strategies.
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摘要  
由禾谷镰孢(Fusarium graminearum)引发的小麦赤霉病是一种重要的农作物真菌病害。禾谷镰孢不仅能够侵染小麦,造成产量降低,还会产生多种毒素,威胁人畜健康,对食品安全构成巨大威胁。禾谷镰孢整个生活史,包括生长、致病、产毒及有性生殖等生命活动都受到了组蛋白乙酰化等修饰的调控。组蛋白乙酰化状态由组蛋白乙酰化复合体(HAT)和去乙酰化复合体(HDAC)共同调节。其中Rpd3复合体作为最重要的组蛋白去乙酰化复合体之一而受到广泛关注。Sin3是Rpd3复合体中最大的亚基,对其关键功能位点及作用机制尚缺乏认识。在本研究中,我们鉴定到位于第810位的谷氨酸残基(E810)是禾谷镰孢FgSin3上的关键位点。研究发现,FgSin3的E810位点突变会引起禾谷镰孢菌丝生长、有性生殖、致病力及DON毒素合成的缺陷。此外,E810K的错义突变能够提高因FNG1(人类生长抑制基因ING1的同源基因)缺失而降低的H4乙酰化水平,从而部分回复fng1突变体的表型缺陷。经序列比对和进化分析,发现FgSin3的同源基因在真核生物中普遍存在,并且其E810功能位点在真菌、动物和植物中表现出高度保守性。基于Alphafold2预测的结构,E810位于FgRpd3-FgSin3的互作界面上,并与FgRpd3的R317位点形成氢键。E810的模拟突变会破坏该氢键的形成,进而影响FgRpd3和FgSin3间的蛋白互作。综上,FgSin3的E810位点可能通过影响Rpd3复合体亚基的组装,与Fng1共同维系真菌组蛋白H4乙酰化平衡,并介导复杂的生物学过程。鉴于FgSin3功能及序列的保守性,以及E810位点周围残基在不同物种中的偏好性差异,未来有望作为药物研发的候选靶标。本研究鉴定到Sin3中的关键功能位点,并从生物学功能、结构基础和进化模式等方面对其参与Rpd3复合体组装的机制和途径进行了解析。


Abstract  

The Rpd3 histone deacetylase complex is a multiple-subunit complex that mediates the regulation of chromatin accessibility and gene expression.  Sin3, the largest subunit of Rpd3 complex, is conserved in a broad range of eukaryotes.  Despite being a molecular scaffold for complex assembly, the functional sites and mechanism of action of Sin3 remain unexplored.  In this study, we functionally characterized a glutamate residue (E810) in FgSin3, the ortholog of yeast Sin3 in Fusarium graminearum (known as wheat scab fungus).  Our findings indicate that E810 was important for the functions of FgSin3 in regulating vegetative growth, sexual reproduction, wheat infection, and DON biosynthesis.  Furthermore, the E810K missense mutation restored the reduced H4 acetylation caused by the deletion of FNG1, the ortholog of the human inhibitor of growth (ING1) gene in Fgraminearum.  Correspondingly, the defects of the fng1 mutant were also partially rescued by the E810K mutation in FgSin3.  Sequence alignment and evolutionary analysis revealed that E810 residue is well-conserved in fungi, animals, and plants.  Based on Alphafold2 structure modeling, E810 localized on the FgRpd3–FgSin3 interface for the formation of a hydrogen bond with FgRpd3.  Mutation of E810 disrupts the hydrogen bond and likely affects the FgRpd3–FgSin3 interaction.  Taken together, E810 of FgSin3 is functionally associated with Fng1 in the regulation of H4 acetylation and related biological processes, probably by affecting the assembly of the Rpd3 complex.  

Keywords:  histone acetylation       ING protein        phytopathogen        Rpd3 histone deacetylase complex  
Received: 11 August 2023   Online: 05 January 2024   Accepted: 14 November 2023
Fund: This research was supported by the grants from the National Natural Science Foundation of China (32102181) and the Shaanxi Science Fund for Distinguished Young Scholars, China (2022JC-14).

About author:  Huaijian Xu, E-mail: huaijianxu@yeah.net; #Correspondence Cong Jiang, E-mail: cjiang@nwafu.edu.cn; Hang Jiang, E-mail: jhfor724@163.com

Cite this article: 

Huaijian Xu, Ruoxuan Jiang, Xianhui Fu, Qinhu Wang, Yutong Shi, Xiaofei Zhao, Cong Jiang, Hang Jiang. 2025. A missense mutation in the Sin3 subunit of Rpd3 histone deacetylase complex bypasses the requirement for FNG1 in wheat scab fungus. Journal of Integrative Agriculture, 24(8): 3087-3094.

Barnes V L, Strunk B S, Lee I, Huttemann M, Pile L A. 2010. Loss of the SIN3 transcriptional corepressor results in aberrant mitochondrial function. BMC Biochemistry11, 26.

Brandao F, Esher S K, Ost K S, Pianalto K, Nichols C B, Fernandes L, Bocca A L, Pocas-Fonseca M J, Alspaugh J A. 2018. HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence. Scientific Reports8, 5209.

Chen C, Chen H, Zhang Y, Thomas H R, Frank M H, He Y, Xia R. 2020. TBtools: An integrative toolkit developed for interactive analyses of big biological data. Molecular Plant13, 1194–1202.

Connolly L R, Smith K M, Freitag M. 2013. The Fusarium graminearum histone H3 K27 methyltransferase KMT6 regulates development and expression of secondary metabolite gene clusters. PLoS Genetics9, e1003916.

Goswami R S, Kistler H C. 2004. Heading for disaster: Fusarium graminearum on cereal crops. Molecular Plant Pathology5, 515–525.

Grzenda A, Lomberk G, Zhang J S, Urrutia R. 2009. Sin3: Master scaffold and transcriptional corepressor. Biochimica et Biophysica Acta1789, 443–450.

Guan H, Wang P, Zhang P, Ruan C, Ou Y, Peng B, Zheng X, Lei J, Li B, Yan C, Li H. 20 23. Diverse modes of H3K36me3-guided nucleosomal deacetylation by Rpd3S. Nature620, 669–675.

Gujral P, Mahajan V, Lissaman A C, Ponnampalam A P. 2020. Histone acetylation and the role of histone deacetylases in normal cyclic endometrium. Reproductive Biology and Endocrinology18, 84.

Guo Z, Chu C, Lu Y, Zhang X, Xiao Y, Wu M, Gao S, Wong C C L, Zhan X, Wang C. 2023. Structure of a SIN3-HDAC complex from budding yeast. Nature Structural & Molecular Biology30, 753–760.

Harris L J, Balcerzak M, Johnston A, Schneiderman D, Ouellet T. 2016. Host-preferential Fusarium graminearum gene expression during infection of wheat, barley, and maize. Fungal Biology120, 111–123.

He G H, Helbing C C, Wagner M J, Sensen C W, Riabowol K. 2005. Phylogenetic analysis of the ING family of PHD finger proteins. Molecular Biology and Evolution22, 104–116.

Jiang C, Cao S, Wang Z, Xu H, Liang J, Liu H, Wang G, Ding M, Wang Q, Gong C, Feng C, Hao C, Xu J R. 2019. An expanded subfamily of G-protein-coupled receptor genes in Fusarium graminearum required for wheat infection. Nature Microbiology4, 1582–1591.

Jiang H, Xia A, Ye M, Ren J, Li D, Liu H, Wang Q, Lu P, Wu C, Xu J R, Jiang C. 2020. Opposing functions of Fng1 and the Rpd3 HDAC complex in H4 acetylation in Fusarium graminearumPLoS Genetics16, e1009185.

Jiang H, Zhang Y, Wang W, Cao X, Xu H, Liu H, Qi J, Jiang C, Wang C. 2022. FgCsn12 is involved in the regulation of ascosporogenesis in the wheat scab fungus Fusarium graminearumInternational Journal of Molecular Sciences23, 10445.

Kong X, Van Diepeningen A D, Van Der Lee T J, Waalwijk C, Xu J, Xu J, Zhang H, Chen W, Feng J. 2018. The Fusarium graminearum histone acetyltransferases are important for morphogenesis, DON biosynthesis, and pathogenicity. Frontiers in Microbiology9, 654.

Letunic I, Bork P. 2021. Interactive tree of life (iTOL) v5: An online tool for phylogenetic tree display and annotation. Nucleic Acids Research49, W293–W296.

Lin C, Cao X, Qu Z, Zhang S, Naqvi N I, Deng Y Z. 2021. The histone deacetylases MoRpd3 and MoHst4 regulate growth, conidiation, and pathogenicity in the rice blast fungus Magnaporthe oryzaemSphere6, e0011821.

Lin C, Wu Z, Shi H, Yu J, Xu M, Lin F, Kou Y, Tao Z. 2022. The additional PRC2 subunit and Sin3 histone deacetylase complex are required for the normal distribution of H3K27me3 occupancy and transcriptional silencing in Magnaporthe oryzaeNew Phytologist236, 576–589.

Marcum R D, Hsieh J, Giljen M, Justice E, Daffern N, Zhang Y, Radhakrishnan I. 2022. A capped Tudor domain within a core subunit of the Sin3L/Rpd3L histone deacetylase complex binds to nucleic acid G-quadruplexes. Journal of Biological Chemistry298, 101558.

Marmorstein R, Zhou M M. 2014. Writers and readers of histone acetylation: Structure, mechanism, and inhibition. Cold Spring Harbor Perspectives in Biology6, a018762.

Mirdita M, Schutze K, Moriwaki Y, Heo L, Ovchinnikov S, Steinegger M. 2022. ColabFold: Making protein folding accessible to all. Nature Methods19, 679–682.

Patel A B, Qing J, Tam K H, Zaman S, Luiso M, Radhakrishnan I, He Y. 2023. Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex. Nature Communications14, 3061.

Pettersen E F, Goddard T D, Huang C C, Meng E C, Couch G S, Croll T I, Morris J H, Ferrin T E. 2021. UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Science30, 70–82.

Ren J, Zhang Y, Wang Y, Li C, Bian Z, Zhang X, Liu H, Xu J R, Jiang C. 2022. Deletion of all three MAP kinase genes results in severe defects in stress responses and pathogenesis in Fusarium graminearumStress Biology2, 6.

Wallace I M, O’sullivan O, Higgins D G, Notredame C. 2006. M-Coffee: Combining multiple sequence alignment methods with T-Coffee. Nucleic Acids Research34, 1692–1699.

Wang C, Guo Z, Chu C, Lu Y, Zhang X, Zhan X. 2023. Two assembly modes for SIN3 histone deacetylase complexes. Cell Discovery9, 42.

Wang C, Zhang S, Hou R, Zhao Z, Zheng Q, Xu Q, Zheng D, Wang G, Liu H, Gao X, Ma J W, Kistler H C, Kang Z, Xu J R. 2011. Functional analysis of the kinome of the wheat scab fungus Fusarium graminearumPLoS Pathogens7, e1002460.

Wang Q, Liu H, Xu H, Hei R, Zhang S, Jiang C, Xu J R. 2019. Independent losses and duplications of autophagy-related genes in fungal tree of life. Environmental Microbiology21, 226–243.

Xu H, Ye M, Xia A, Jiang H, Huang P, Liu H, Hou R, Wang Q, Li D, Xu J R, Jiang C. 2022. The Fng3 ING protein regulates H3 acetylation and H4 deacetylation by interacting with two distinct histone-modifying complexes. New Phytologist235, 2350–2364.

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