The CFEM (Common in Fungal Extracellular Membrane) domain defines a family of cysteine-rich proteins unique to fungi, playing pivotal roles in host-pathogen interactions. However, the repertoire and functions of CFEM proteins in the broad-host-range necrotrophic pathogen Sclerotinia sclerotiorum remain largely unexplored. Through genome-wide bioinformatic analysis, we identified 13 CFEM-containing proteins (SsCFEM1-13) in S. sclerotiorum. Characterization revealed substantial diversity in their physicochemical properties, domain architecture, and predicted subcellular localization. Ten proteins possess a secretion signal, with six predicted to be GPI-anchored and three classified as high-confidence effectors. Members lacking transmembrane domains were predicted to adopt the conserved CFEM "helical-basket" fold. Phylogenetic analysis grouped SsCFEMs into two distinct clades and indicated a complex evolutionary history involving both conserved ancestry and lineage-specific expansion. Transcriptomic profiling showed that most genes were upregulated during early infection of various host plants, with SsCFEM8 exhibiting particularly strong and consistent induction. Crucially, transient expression assays in Nicotiana benthamiana revealed that several SsCFEM proteins, notably SsCFEM4 and SsCFEM9, function as cell death suppressors, validating their predicted effector roles and identifying key virulence candidates. This study provides the first comprehensive catalog and functional prediction of the CFEM protein family in S. sclerotiorum, establishing a foundation for future mechanistic studies on their roles in the pathogenesis of this devastating fungal pathogen.

Plants deploy intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors to detect pathogen-secreted virulence effectors and trigger defense responses. NLRs recognize effectors from both adapted and non-adapted pathogens (Dong et al., 2025), either through direct binding or by monitoring effector-induced modifications of host targets (Cesari et al., 2018). Despite these advances, the mechanism by which NLRs evolve new effector-recognition specificities remains a fundamental question in plant immunity. Recently, Gómez de la Cruz et al. (2026) uncovered a novel evolutionary strategy underlying the recognition of the blast fungus effector Pwl2 by the barley NLR MLA3, in which MLA3 acts as a molecular mimic of the effector’s virulence target, the heavy metal-associated protein HIPP43 (Zdrzałek et al., 2024; Were et al., 2025). Importantly, the authors successfully transferred this molecular mimicry interface into the wheat stem rust resistance protein SR50, generating a chimeric NLR receptor with dual pathogen-recognition capabilities. The engineered receptor conferred resistance to both wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), and rice blast disease, caused by Magnaporthe oryzae, in transgenic barley, highlighting the potential of this strategy for developing broad-spectrum and durable disease resistance in crops.

To safely control crop diseases, development and application of nanomaterials is regarded as a dominant trend in plant protection. Phytic acid (PA), the main storage form of phosphorus in crop seeds, has been widely used as an inhibitor of foodborne bacterial pathogens. However, whether PA can be developed into an anti-plant pathogens nanomaterial is unclear. Herein, to increase PA's cellular permeability, we developed PA-polymerized carbon dots (PCDs), which have an average diameter of about 3 nm and emit autofluorescence. PCDs inhibited rice blast fungus growth by targeting actin filament and depolarizing the mycelial cells. Moreover, PCDs, compared with PA, also showed high efficiency in inhibiting rice blight bacterium by disrupting the cell membrane integrity. Notably, PCDs possessed broad-spectrum antifungal and antibacterial activities, and could be applied as a protective agent to control various crop diseases. Therefore, our results provide a strategy for managing plant diseases by utilizing the PA nanomaterial.

The mitotic exit network (MEN), regulated by the small GTPase Tem1, plays a crucial role in coordinating cytokinesis and cell cycle progression in eukaryotes. In this study, we identified MoTem1, a functional homolog of Saccharomyces cerevisiae Tem1, in the rice blast fungus Magnaporthe oryzae, and investigated its role in mitotic regulation and pathogenesis. Using targeted mutagenesis, we generated a series of mutant strains: ΔMotem1 (knockout), MoTem1-OE (overexpression), as well as MoTem1-CA (constitutively active) and MoTem1-DN (dominant-negative) variants created via single-nucleotide substitutions. Phenotypic characterization revealed that MoTem1’s activity states are critical for fungal growth, development, stress tolerance, and pathogenicity. While ΔMotem1 and MoTem1-CA strains showed reduced virulence, the MoTem1-DN mutant exhibited hypervirulence. Transcriptomic profiling and weighted gene co-expression network analysis (WGCNA) identified chitin synthase MoCHS1 as a downstream gene whose expression is directly or indirectly influenced by MoTem1 activity states. Pharmacological inhibition of chitin synthesis using Polyoxin B in MoTem1-CA showed increased sensitivity, confirming a decreased expression of chitin synthase in the MoTem1-CA strain. Subcellular localization studies revealed GTP-dependent spindle pole body (SPB) targeting, with inactive MoTem1 failing to localize to SPBs, while constitutive MEN activation in MoTem1-CA disrupted spindle position checkpoint (SPOC) controls, resulting in multinucleate hyphae and a range of developmental defects. In conclusion, our work establishes MoTem1 not merely as a cell cycle regulator, but as a global upstream factor that influences nuclear division, cell wall integrity, and broadly reshapes the genomic regulatory network to govern development and pathogenesis in M. oryzae.

Mad2, a conserved core component of the spindle assembly checkpoint (SAC) in eukaryotes, delays anaphase onset in case of incorrect kinetochore-microtubule attachment. However, its functions in plant-pathogenic fungi remain largely unknown. Here, we identified the Mad2 homologue in rice blast fungus Magnaporthe oryzae (MoMad2), which shows high similarity with Mad2 in fission yeast. When expressed in fission yeast, MoMad2 associated with native SpMad1 and SpCdc20, and successfully rescued the ΔSpmad2 mutant's defect in arresting anaphase onset upon damaged spindle, indicating the conserved SAC function of MoMad2. Moreover, MoMad2 interacted with MoMad1 and depends on MoMad1 for its nuclear envelope-localisation. Although it plays a dispensable role in M. oryzae growth, MoMad2 is required for tolerance to the microtubule depolymerising agent treatment. ΔMomad2 mutants exhibited shorter hyphal compartments and earlier conidial germination and appressorium formation, suggesting that MoMad2 deletion shortens M. oryzae's mitotic cell cycle due to defective SAC arrest. Additionally, knockout of MoMAD2 decreased the appressorial turgor pressure, impaired appressorium penetration and compromised M. oryzae pathogenicity. Taken together, our findings revealed that MoMad2, as a conserved component in SAC signalling, is essential for full pathogenicity of rice blast fungus.

Fungal innate immunity resembles mammalian innate immunity. It does not employ toll-like receptors (TLRs), but should employ endocytosis of non-fungal molecular patterns recognized by nuclear-localizing receptors (NLR). Downstream, both types of receptors are Mammalian Ste20 kinases (MSTs). We identified an MST3 ortholog in the plant pathogens Fusarium graminearum ( FgMST3 ) and Magnaporthe oryzae ( MoMST3 ). We knocked out both genes and investigated mutants using a standard panel of tests for growth, development, and pathogenicity for the respective fungi. Both ΔFgMST3 and ΔMoMST3 strains showed reduced pathogenicity. The deletions negatively affected conidia production and conidia germination but had little effect on growth rate. However, the two mutants reacted differently to various stress treatments, especially to Zn2+ and gentamicin. In addition, we constructed an innate immunity reporter system for F. graminearum to detect less than 4-hour responses to non-self-molecular patterns (NSMP) like bacterial outer membrane vesicles (OMVs) and trace levels of sucrose, indicating plant. The reporter gene responses to OMVs of MST3 mutant strains are severely reduced. Our results indicate that both MoMst3 and FgMst3 are involved in fungal innate immunity downstream of unknown NLR proteins, motivating studies to identify genes for the NLR receptors. Finding such and investigating how they work and vary between fungal species and strains should be essential for understanding fungal biotic interactions with viruses, bacteria, plants, and animals. ### Competing Interest Statement The authors have declared no competing interest.

Unique genes refer to genes specific to a particular organism and play crucial roles in the biological functions, evolutionary processes, and adaptations to external environments. However, the roles of unique genes in plant pathogenic fungi remain largely unexplored. In this study, we identified a novel unique gene in the rice blast fungus Magnaporthe oryzae, named MoUNG (M. oryzae unique gene), through T-DNA insertion mutagenesis. The disruption of the MoUNG promoter region in the T-DNA insertion mutant (T30-104) led to an almost loss of MoUNG expression. MoUNG has no functional domains and lacks homologues in other organism. It is highly expressed during the early-infection stage between 16 and 32 h post-inoculation (HPI), in contrast to its expression in mycelia and at the later infection stage of 48 HPI. Notably, attempts to knock out MoUNG were unsuccessful, so we examined the T30-104 mutant and found it showed significantly reduced growth, conidiation, and pathogenicity. Introducing the full-length MoUNG with its promoter into T30-104 restored these phenotypic defects. Additionally, subcellular localization assays revealed that MoUNG exhibits a dot-like distribution within the cytoplasm of mycelium, conidium, appressorium, and invasive hypha. Furthermore, knock-down of MoUNG produced results similar to those observed with the insertion mutation. In conclusion, we identified a novel unique gene MoUNG in M. oryzae and demonstrated its involvement in growth, conidiation, and pathogenicity.

Plant lectins have a significant impact on the defense against pathogens and insect attacks. The jacalin-related lectin OsMbl1 from rice (Oryza sativa L.) has been reported to play a crucial role in pattern-triggered immunity (PTI). However, the underlying mechanism remains unclear. In this study, we identified a GDSL-like lipase, OsGdsl1, that interacts with OsMbl1 both in vitro and in vivo. The OsGdsl1 protein, which has lipase activity, is localized in the lipid bodies and apoplast. The expression of OsGDSL1 is modulated upon exposure to Magnaporthe oryzae (M. oryzae) or plant hormones. Deletion of the OsGDSL1 gene not only improved the resistance of rice to M. oryzae, but also led to an increased ROS burst after chitin treatments. The expression of some pathogenesis-related (PR) genes was upregulated in the mutants. We also found that OsMbl1 inhibited the lipase activity of OsGdsl1 during infection with M. oryzae. Overall, our results suggest that OsGdsl1 negatively regulates rice immunity to M. oryzae infection by downregulating ROS bursts and PR gene expressions, while its lipase activity, which is inhibited by OsMbl1, contributes to the enhancement of rice innate immunity during M. oryzae infection.

The Myb family of transcription factors (TFs) is a large and functionally diverse group found in all eukaryotes. Its role in fungi remains poorly studied, despite the fact that it is thought to play a role in the pathogenicity of fungal pathogens. In this study, we have characterized the functional role of a Myb family TF called MoMyb13 in the rice blast fungus, Magnaporthe oryzae. MoMyb13 has orthologues only in ascomycete fungi, making it of special interest. Localization experiments confirmed that MoMyb13 is located in the nuclei, as expected for a TF. Phenotypic analysis showed that MoMyb13 mutants exhibited reduced growth, white instead of dark colonies, formed no conidia and, consequently, no conidial appressoria. The mutants completely lost pathogenicity, despite being able to form dark hyphal appressoria at their hyphae ends. Furthermore, the mutant colonies lost hydrophobicity and had significantly reduced expression of the hydrophobin MPG1 that MoMyb13 appears to regulate. However, overexpression of MPG1 in the mutants restored hydrophobicity, but not pathogenicity. Stress assay showed that the mutants were more sensitive to SDS, CR, and H2O2, but more tolerant to NaCl and SOR. In summary, our study revealed the crucial function of MoMyb13 in the growth, conidiation, hydrophobicity, stress response, and pathogenicity of M. oryzae. MoMyb13 is thus needed in the late and very early stages of infection for the spreading of the fungus to other plants and the early establishment of infection in other plants.

Isw2 proteins, ubiquitous across eukaryotes, exhibit a propensity for DNA binding and exert dynamic influences on local chromosome condensation in an ATP-dependent fashion, thereby modulating the accessibility of neighboring genes to transcriptional machinery. Here, we report the deletion of a putative MoISW2 gene, yielding substantial ramifications on plant pathogenicity. Subsequent gene complementation and chromatin immunoprecipitation sequencing (ChIP-seq) analyses were conducted to delineate binding sites. RNA sequencing (RNA-seq) assays revealed discernible impacts on global gene regulation along chromosomes in both mutant and wild-type strains, with comparative analyses against 55 external RNA-seq data sets corroborating these findings. Notably, MoIsw2-mediated binding and activities delineate genomic loci characterized by pronounced gene expression variability proximal to MoIsw2 binding sites, juxtaposed with comparatively stable expression in surrounding regions. The contingent genes influenced by MoIsw2 activity predominantly encompass niche-determinant genes, including those encoding secreted proteins, secondary metabolites, and stress-responsive elements, alongside avirulence genes. Furthermore, our investigations unveil a spatial correlation between MoIsw2 binding motifs and known transposable elements (TEs), suggesting a potential interplay wherein TE transposition at these loci could modulate the transcriptional landscape of Magnaporthe oryzae in a strain-specific manner. Collectively, these findings position MoIsw2 as a plausible master regulator orchestrating the delicate equilibrium between genes vital for biomass proliferation, akin to housekeeping genes, and niche-specific determinants crucial for ecological adaptability. Stress-induced TE transposition, in conjunction with MoIsw2 activity, emerges as a putative mechanism fostering enhanced mutagenesis and accelerated evolution of niche-determinant genes relative to housekeeping counterparts.IMPORTANCEIsw2 proteins are conserved in plants, fungi, animals, and other eukaryotes. We show that a fungal Isw2 protein in the rice pathogen Magnaporthe oryzae binds to retrotransposon (RT) DNA motifs and affects the epigenetic gene expression landscape of the fungal genome. Mainly ecological niche determinant genes close to the binding motifs are affected. RT elements occur frequently in DNA between genes in most organisms. They move place and multiply in the genome, especially under physiological stress. We further discuss the Isw2 and RT combined activities as a possible sought-after mechanism that can cause biased mutation rates and faster evolution of genes necessary for reacting to abiotic and biotic challenges. The most important biotic challenges for plant pathogens are the ones from the host plants' innate immunity. The overall result of these combined activities will be an adaptation-directed evolution of niche-determinant genes.

Rice blast disease, caused by the fungus Magnaporthe oryzae, is a significant threat to rice production. Resistant cultivars can effectively resist the invasion of M. oryzae. Thus, the identification of disease-resistant genes is of utmost importance for improving rice production. Autophagy, a cellular process that recycles damaged components, plays a vital role in plant growth, development, senescence, stress response, and immunity. To understand the involvement of autophagy-related genes (ATGs) in rice immune response against M. oryzae, we conducted a comprehensive analysis of 37 OsATGs, including bioinformatic analysis, transcriptome analysis, disease resistance analysis, and protein interaction analysis. Bioinformatic analysis revealed that the promoter regions of 33 OsATGs contained cis-acting elements responsive to salicylic acid (SA) or jasmonic acid (JA), two key hormones involved in plant defense responses. Transcriptome data showed that 21 OsATGs were upregulated during M. oryzae infection. Loss-of-function experiments demonstrated that OsATG6c, OsATG8a, OsATG9b, and OsATG13a contribute to rice blast resistance. Additionally, through protein interaction analysis, we identified five proteins that may interact with OsATG13a and potentially contribute to plant immunity. Our study highlights the important role of autophagy in rice immunity and suggests that OsATGs may enhance resistance to rice blast fungus through the involvement of SA, JA, or immune-related proteins. These findings provide valuable insights for future efforts in improving rice production through the identification and utilization of autophagy-related genes.

The Myb family of transcription factors (TFs) is a large and functionally diverse group found in all eukaryotes, but its role in fungi remains poorly understood. Here, we characterized a Myb family TF called MoMyb13 in the rice blast fungus, Magnaporthe oryzae. MoMyb13 has two Myb domains and has orthologues only in ascomycete fungi. Localization experiments confirmed that MoMyb13 is located in the nuclei, as expected for a TF. Phenotypic analysis showed that MoMyb13 mutants exhibited reduced growth, whitened colony appearance and no conidia formation. Importantly, these mutants completely lost pathogenicity, despite being able to form appressoria at their hyphae ends, suggesting that these appressoria were non-functional for causing infection. Furthermore, the mutant colonies lost hydrophobicity and had significantly reduced expression of the hydrophobin MPG1. However, overexpression of MPG1 in the mutants restored their hydrophobicity, but not pathogenicity. Stress assay showed that the mutants were more sensitive to SDS, CR and H2O2, but more tolerant to NaCl and SOR. In summary, our study revealed the essential role of the MoMyb13 in the growth, conidiation, hydrophobicity, stress response and pathogenicity of M. oryzae, and provides valuable insights into the working mechanism of Myb TFs in fungi.

The conserved DNA damage repair complex, MMS21-SMC5/6 (Methyl methane sulfonate 21 - Structural maintenance of chromosomes 5/6), has been extensively studied in yeast, animals, and plants. However, its role in phytopathogenic fungi, particularly in the highly destructive rice blast fungus Magnaporthe oryzae, remains unknown. In this study, we functionally characterized the homologues of this complex, MoMMS21 and MoSMC5, in M. oryzae. We first demonstrated the importance of DNA damage repair in M. oryzae by showing that the DNA damage inducer phleomycin inhibited vegetative growth, infection-related development and pathogenicity in this fungus. Additionally, we discovered that MoMMS21 and MoSMC5 interacted in the nuclei, suggesting that they also function as a complex in M. oryzae. Gene deletion experiments revealed that both MoMMS21 and MoSMC5 are required for infection-related development and pathogenicity in M. oryzae, while only MoMMS21 deletion affected growth and sensitivity to phleomycin, indicating its specific involvement in DNA damage repair. Overall, our results provide insights into the roles of MoMMS21 and MoSMC5 in M. oryzae, highlighting their functions beyond DNA damage repair.

The spindle assembly checkpoint (SAC) proteins are conserved among eukaryotes safeguarding chromosome segregation fidelity during mitosis. However, their biological functions in plant-pathogenic fungi remain largely unknown. In this study, we found that the SAC protein MoMad1 in rice blast fungus (Magnaporthe oryzae) localizes on the nuclear envelope and is dispensable for M. oryzae vegetative growth and tolerance to microtubule depolymerizing agent treatment. MoMad1 plays an important role in M. oryzae infection-related development and pathogenicity. The monopolar spindle 1 homologue in M. oryzae (MoMps1) interacts with MoMad1 through its N-terminal domain and phosphorylates MoMad1 at Ser-18, which is conserved within the extended N termini of Mad1s from fungal plant pathogens. This phosphorylation is required for maintaining MoMad1 protein abundance and M. oryzae full virulence. Similar to the deletion of MoMad1, treatment with Mps1-IN-1 (an Mps1 inhibitor) caused compromised appressorium formation and decreased M. oryzae virulence, and these defects were dependent on its attenuating MoMad1 Ser-18 phosphorylation. Therefore, our study indicates the function of Mad1 in rice blast fungal pathogenicity and sheds light on the potential of blocking Mad1 phosphorylation by Mps1 to control crop fungal diseases.

The family of phosphatidylinositol transfer proteins (PITPs) is able to bind specific lipids to carry out various biological functions throughout different stages of plant life. But the function of PITPs in rice plant is unclear. In this study, 30 PITPs were identified from rice genome, which showed differences in physicochemical properties, gene structure, conservation domains, and subcellular localization. The promoter region of the OsPITPs genes included at least one type of hormone response element, such as methyl jasmonate (Me JA) and salicylic acid (SA). Furthermore, the expression level of OsML-1, OsSEC14-3, OsSEC14-4, OsSEC14-15, and OsSEC14-19 genes were significantly affected by infection of rice blast fungus Magnaporthe oryzae. Based on these findings, it is possible that OsPITPs may be involved in rice innate immunity in response to M. oryzae infection through the Me JA and SA pathway.

Arms race co-evolution of plant-pathogen interactions evolved sophisticated recognition mechanisms between host immune receptors and pathogen effectors. Different allelic haplotypes of an immune receptor in the host mount distinct recognition against sequence or non-sequence related effectors in pathogens. We report the molecular characterization of the Piks allele of the rice immune receptor Pik against rice blast pathogen, which requires two head-to-head arrayed nucleotide-binding sites and leucine-rich repeat proteins. Like other Pik alleles, both Piks-1 and Piks-2 are necessary and sufficient for mediating resistance. However, unlike other Pik alleles, Piks does not recognize any known AvrPik variants of Magnaporthe oryzae. Sequence analysis of the genome of an avirulent isolate V86010 further revealed that its cognate avirulence (Avr) gene most likely has no significant sequence similarity to known AvrPik variants. Piks-1 and Pikm-1 have only two amino acid differences within the integrated heavy metal-associated (HMA) domain. Pikm-HMA interacts with AvrPik-A, -D, and -E in vitro and in vivo, whereas Piks-HMA does not bind any AvrPik variants. Characterization of two amino acid residues differing Piks-1 from Pikm-1 reveal that Piks-E229Q derived from the exchange of Glu229 to Gln229 in Piks-1 gains recognition specificity against AvrPik-D but not AvrPik-A or -E, indicating that Piks-E229Q partially restores the Pikm spectrum. By contrast, Piks-A261V derived from the exchange of Ala261 to Val261 in Piks-1 retains Piks recognition specificity. We conclude that Glu229 in Piks-1 is critical for Piks breaking the canonical Pik/AvrPik recognition pattern. Intriguingly, binding activity and ectopic cell death induction is maintained between Piks-A261V and AvrPik-D, implying that positive outcomes from ectopic assays might be insufficient to deduce its immune activity against the relevant effectors in rice and rice blast interaction.

EDITORIAL article Front. Fungal Biol., 13 June 2023Sec. Fungal Pathogenesis Volume 4 - 2023 | https://doi.org/10.3389/ffunb.2023.1231925

Isw2 proteins are conserved in eukaryotes and are known to bind to DNA and dynamically influence local chromosome condensation close to their DNA binding site in an ATP-dependent manner making genes close to the binding sites more accessible for transcription and repression. A putative MoISW2 gene was deleted with large effects on plant pathogenicity as a result. The gene was complemented and a ChIP-sec was performed to identify binding sites. RNAsec showed effects on the overall regulation of genes along the chromosomes for mutant and background strains and this was compared with RNAseq from 55 downloaded RNA-seq datasets from the same strain and found similar. MoIsw2 binding and activities create genomic regions affected by MoIsw2 with high gene expression variability close to the MoIsw2 binding sites while surrounding regions have lower gene expression variability. The genes affected by the MoIsw2 activity are niche-determinant genes (secreted proteins, secondary metabolites and stress-coping genes) and avirulence genes. We further show that MoIsw2 binding sites with the DNA binding motifs coincide with known transposable elements (TE) making it likely that TE-transposition at the binding sites can affect the transcription profile of M. oryze in a strain-specific manner. We conclude that MoIsw2 is a likely candidate for a master regulator, regulating the dynamic balance between biomass growth genes (like housekeeping genes) and nich-determinant genes important for ecological fitness. Stress-induced TE transposition is together with MoIsw2 activity a likely mechanism creating more mutations and faster evolution of the niche-determinant genes than for housekeeping genes.### Competing Interest StatementThe authors have declared no competing interest.

AbstractThe initial stage of rice blast fungus, Magnaporthe oryzae, infection, before 36 h postinoculation, is a critical timespan for deploying pathogen effectors to overcome the host's defences and ultimately cause the disease. However, how this process is regulated at the transcription level remains largely unknown. This study functionally characterized two M. oryzae Early Infection‐induced Transcription Factor genes (MOEITF1 and MOEITF2) and analysed their roles in this process. Target gene deletion and mutant phenotype analysis showed that the mutants Δmoeitf1 and Δmoeitf2 were only defective for infection growth but not for vegetative growth, asexual/sexual sporulation, conidial germination, and appressoria formation. Gene expression analysis of 30 putative effectors revealed that most effector genes were down‐regulated in mutants, implying a potential regulation by the transcription factors. Artificial overexpression of two severely down‐regulated effectors, T1REP and T2REP, in the mutants partially restored the pathogenicity of Δmoeitf1 and Δmoeitf2, respectively, indicating that these are directly regulated. Yeast one‐hybrid assay and electrophoretic mobility shift assay indicated that Moeitf1 specifically bound the T1REP promoter and Moeitf2 specifically bound the T2REP promoter. Both T1REP and T2REP were predicted to be secreted during infection, and the mutants of T2REP were severely reduced in pathogenicity. Our results indicate crucial roles for the fungal‐specific Moeitf1 and Moeitf2 transcription factors in regulating an essential step in M. oryzae early establishment after penetrating rice epidermal cells, highlighting these as possible targets for disease control.

Abstract Isw2 binds DNA using a Myb-type DNA binding domain, interacts with histones (especially His4) in the closest nucleosome, and regulates gene access by the nucleosome limited-sliding mechanism resulting in lower access to DNA close to the binding site and better access in the immediate surroundings. We had previously made a GFP complementation of the potential MoIsw2 and first confirmed that MoISW2 is co-regulated with MoHIS4. ChIP-seq found DNA binding sites, and a common palindromic motif was identified in about 200 sequences that, in addition, were in retrotransposon sequences where most avirulence genes are. These were downregulated in the background strain compared to DMoisw2, while further away from the binding site, the absolute difference in regulation was higher and varied in a wave-like pattern as expected for the limited sliding-type mechanism. The avirulence genes downregulation in two M. oryzae isolates were compared and confirmed. Finally, we found that most genes differentially upregulated in the DMoisw2 mutant regulate biomass growth. In contrast, the ones downregulated have to do with mainly niche adaptations and niche fitness. MoIsw2 retrotransposon binding and actions lay a possible mechanistic ground for a natural adaptation-directed fast evolution (NADFE) of M. oryzae, a new concept for Eukaryotes.