The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in Aspergillus fumigatus
<p>Molecular structures of KdmA and KdmB. (<b>A</b>) Schematic presentation of the domain structures of the KdmA and KdmB proteins using SMART (<a href="http://smart.embl-heidelberg.de" target="_blank">http://smart.embl-heidelberg.de</a>, accessed on 4 April 2021). (<b>B</b>) Multiple sequence alignment of the JmjC domains of demethylases from <span class="html-italic">A. nidulans</span> (AN), <span class="html-italic">A. fumigatus</span> (Afu), <span class="html-italic">A. niger</span> (An), <span class="html-italic">A. flavus</span> (AFL), and <span class="html-italic">A. oryzae</span> (AO). Conserved residues responsible for α-ketoglutarate and Fe (II) binding sites are marked in green and blue, respectively. (<b>C</b>) A phylogenetic tree of demethylase-like proteins in various <span class="html-italic">Aspergillus</span> species constructed based on the matrix of neighbor-joining distances between the JmjC domain sequences. (<b>D</b>) Western blot with antibody specific to histone H3, H3K4me3, and H3K36me3 antibodies. Relative intensities are shown below. Statistical significance of differences was assessed by Student’s <span class="html-italic">t</span>-test: ** <span class="html-italic">p</span> < 0.01.</p> "> Figure 2
<p>KdmA and KdmB regulate normal growth and asexual development in different ways. (<b>A</b>) Colony photographs and growth of WT, Δ<span class="html-italic">kdmA</span>, and Δ<span class="html-italic">kdmB</span> strains point-inoculated on various solid media and grown in solid glucose minimal medium with 0.1% yeast extract (MMY), 10 g/L yeast extract + 30 g/L glucose (YG), or potato dextrose agar (PDA) for 3 days and determined colony diameter. (<b>B</b>) Conidia numbers produced by each strain per plate. (<b>C</b>) Transcript levels of the key asexual developmental regulators in the mutants relative to the corresponding level in the WT strain at 3 days determined by quantitative RT-PCR (RT-qPCR). Dot line indicates the level of WT transcript. Fungal cultures were grown in MMY, and mRNA levels were normalized to the expression level of the <span class="html-italic">ef1α</span> gene. Statistical significance of differences was assessed by Student’s <span class="html-italic">t</span>-test: * <span class="html-italic">p</span> < 0.05, ** <span class="html-italic">p</span> < 0.01.</p> "> Figure 3
<p>Distinct responses of Δ<span class="html-italic">kdmA</span> and Δ<span class="html-italic">kdmB</span> mutants to various kinds of oxidative stress. (<b>A</b>) Heatmap of altered expression levels of genes encoding oxidative stress-related proteins in Δ<span class="html-italic">kdmA</span> and Δ<span class="html-italic">kdmB</span> mutants. (<b>B</b>) Colony appearance and radial growth inhibition after inoculation of 1 × 10<sup>5</sup> conidia on solid YG medium containing oxidative stressors. (<b>C</b>) Catalase activity of the WT and mutant strains. (<b>D</b>) SOD activity of the WT and mutant strains shown in non-denaturing polyacrylamide gels. Relative intensities of each enzyme’s activity are shown below. Statistical significance of differences between WT and mutant strains was evaluated using Student’s <span class="html-italic">t</span>-test: ** <span class="html-italic">p</span> < 0.01.</p> "> Figure 4
<p>Increased sensitivity of the Δ<span class="html-italic">kdmA</span> and Δ<span class="html-italic">kdmB</span> mutants to 6AU. (<b>A</b>) Radial growth of the WT and mutant strains in the presence of chromatin-targeting inhibitors. (<b>B</b>) RT-qPCR analysis of expression levels of the 6AU resistance-related genes <span class="html-italic">imd2</span> and <span class="html-italic">sdt2</span> in the WT and mutant strains in the presence of 100 μg/mL of AU. Dot line indicates the level of WT transcript. Statistical significance of differences between WT and mutant strains was evaluated using Student’s <span class="html-italic">t</span>-test: ** <span class="html-italic">p</span> < 0.01.</p> "> Figure 5
<p>Roles of KdmA and KdmB in the production of gliotoxin (GT) and other putative secondary metabolites. (<b>A</b>) Heatmap of altered expression levels of genes encoding secondary metabolite biosynthesis in mutant strains. (<b>B</b>) Determination of GT production and several secondary metabolites in the WT and mutant strains. Standard GT concentration was 10 μg (left side) and 5 μg (right side). Left: a representative thin-layer chromatogram of the culture supernatant of each strain extracted with chloroform. Right: a graph of relative intensities of individual chromatogram bands in culture supernatants from different strains. (<b>C</b>) RT-qPCR analysis of changes the <span class="html-italic">laeA</span> and <span class="html-italic">gliZ</span> gene expression levels in mutant strains compared to that in the WT strain. Dot line indicates the level of WT transcript. Statistical significance of differences between WT and mutant strains was assessed by Student’s <span class="html-italic">t</span>-test: * <span class="html-italic">p</span> < 0.05, ** <span class="html-italic">p</span> < 0.01.</p> "> Figure 6
<p>Effects of KdmA and KdmB on <span class="html-italic">A. fumigatus</span> virulence. (<b>A</b>) Survival curves of mice intranasally administered with PBS or with conidia of the WT or one of the mutant strains (n = 10/group). (<b>B</b>) Representative lung sections of mice from different experimental groups stained with hematoxylin and eosin (H&E) or periodic acid–Schiff reagent (PAS). Arrows indicate fungal mycelium. Scale bar = 50 µm. (<b>C</b>) Fungal burden in the lungs of mice infected with the WT or one of the mutant strains. Statistical significance of differences between WT and mutant strains was evaluated by Student’s <span class="html-italic">t</span>-test: ** <span class="html-italic">p</span> < 0.01.</p> "> Figure 7
<p>Genome-wide expression analyses of the Δ<span class="html-italic">kdmA</span> and Δ<span class="html-italic">kdmB</span>. (<b>A</b>) Volcano plot showing the fold change (x-axis) and <span class="html-italic">p</span>-value (y-axis) of genes sequenced in Δ<span class="html-italic">kdmA</span> (upper) and Δ<span class="html-italic">kdmB</span> (lower). Red and green dots denote up- and downregulated genes, respectively. (<b>B</b>) Functional annotation histograms of DEGs in Δ<span class="html-italic">kdmA</span> (upper) and Δ<span class="html-italic">kdmB</span> (lower). The red bars represent genes whose mRNA levels increased in the mutant, whereas the green bars represent those genes whose mRNA levels decreased in the mutant strain.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bioinformatic Analysis of KdmA and KdmB
2.2. Strains and Culture Conditions
2.3. Construction of Mutant A. fumigatus Strains
2.4. Nucleic Acid Isolation and Manipulation
2.5. Physiological Experiments
2.6. Enzyme Assay and Western Blotting
2.7. Transcriptome Analysis
2.8. Murine Virulence Assay
2.9. Statistical Analysis
3. Results
3.1. Structure of KdmA and KdmB of A. fumigatus
3.2. KdmA and KdmB Influence Vegetative Growth and Asexual Sporulation
3.3. KdmA and KdmB Affect Response to Oxidative Stress
3.4. KdmA and KdmB Regulate Sensitivity to 6-Azauracil
3.5. KdmA and KdmB Oppositely Affect Gliotoxin Synthesis
3.6. Virulence of the ΔkdmA and ΔkdmB Strains in Immunocompromised Mice
3.7. Transcriptome Analysis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Mosammaparast, N.; Shi, Y. Reversal of histone methylation: Biochemical and molecular mechanisms of histone demethylases. Annu. Rev. Biochem. 2010, 79, 155–179. [Google Scholar] [CrossRef]
- Kouzarides, T. Chromatin modifications and their function. Cell 2007, 128, 693–705. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gardner, K.E.; Allis, C.D.; Strahl, B.D. Operating on chromatin, a colorful language where context matters. J. Mol. Biol. 2011, 409, 36–46. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bannister, A.J.; Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res. 2011, 21, 381–395. [Google Scholar] [CrossRef] [PubMed]
- Shwab, E.K.; Bok, J.W.; Tribus, M.; Galehr, J.; Graessle, S.; Keller, N.P. Histone deacetylase activity regulates chemical diversity in Aspergillus. Eukaryot. Cell 2007, 6, 1656–1664. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Strauss, J.; Reyes-Dominguez, Y. Regulation of secondary metabolism by chromatin structure and epigenetic codes. Fungal Genet. Biol. 2011, 48, 62–69. [Google Scholar] [CrossRef] [Green Version]
- Gacek-Matthews, A.; Noble, L.M.; Gruber, C.; Berger, H.; Sulyok, M.; Marcos, A.T.; Strauss, J.; Andrianopoulos, A. KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans. Mol. Microbiol. 2015, 96, 839–860. [Google Scholar] [CrossRef] [Green Version]
- Gacek, A.; Strauss, J. The chromatin code of fungal secondary metabolite gene clusters. Appl. Microbiol. Biotechnol. 2012, 95, 1389–1404. [Google Scholar] [CrossRef] [Green Version]
- Klose, R.J.; Kallin, E.M.; Zhang, Y. JmjC-domain-containing proteins and histone demethylation. Nat. Rev. Genet. 2006, 7, 715–727. [Google Scholar] [CrossRef]
- Dimitrova, E.; Turberfield, A.H.; Klose, R.J. Histone demethylases in chromatin biology and beyond. EMBO Rep. 2015, 16, 1620–1639. [Google Scholar] [CrossRef]
- Shi, Y.G.; Tsukada, Y. The discovery of histone demethylases. Cold Spring Harb. Perspect. Biol. 2013, 5, a017947. [Google Scholar] [CrossRef] [Green Version]
- Gacek-Matthews, A.; Berger, H.; Sasaki, T.; Wittstein, K.; Gruber, C.; Lewis, Z.A.; Strauss, J. KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans. PLoS Genet. 2016, 12, e1006222. [Google Scholar] [CrossRef] [PubMed]
- Barski, A.; Cuddapah, S.; Cui, K.; Roh, T.Y.; Schones, D.E.; Wang, Z.; Wei, G.; Chepelev, I.; Zhao, K. High-resolution profiling of histone methylations in the human genome. Cell 2007, 129, 823–837. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Quan, Z.; Oliver, S.G.; Zhang, N. JmjN interacts with JmjC to ensure selective proteolysis of Gis1 by the proteasome. Microbiology 2011, 157, 2694–2701. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, F.; Chandrasekharan, M.B.; Chen, Y.C.; Bhaskara, S.; Hiebert, S.W.; Sun, Z.W. The JmjN domain of Jhd2 is important for its protein stability, and the plant homeodomain (PHD) finger mediates its chromatin association independent of H3K4 methylation. J. Biol. Chem. 2010, 285, 24548–24561. [Google Scholar] [CrossRef] [Green Version]
- Brookman, J.L.; Denning, D.W. Molecular genetics in Aspergillus fumigatus. Curr. Opin. Microbiol. 2000, 3, 468–474. [Google Scholar] [CrossRef]
- Kafer, E. Meiotic and mitotic recombination in Aspergillus and its chromosomal aberrations. Adv. Genet. 1977, 19, 33–131. [Google Scholar]
- Palmer, J.M.; Perrin, R.M.; Dagenais, T.R.; Keller, N.P. H3K9 methylation regulates growth and development in Aspergillus fumigatus. Eukaryot. Cell 2008, 7, 2052–2060. [Google Scholar] [CrossRef] [Green Version]
- Xue, T.; Nguyen, C.K.; Romans, A.; Kontoyiannis, D.P.; May, G.S. Isogenic auxotrophic mutant strains in the Aspergillus fumigatus genome reference strain AF293. Arch. Microbiol. 2004, 182, 346–353. [Google Scholar] [CrossRef]
- Yu, J.H.; Hamari, Z.; Han, K.H.; Seo, J.A.; Reyes-Dominguez, Y.; Scazzocchio, C. Double-joint PCR: A PCR-based molecular tool for gene manipulations in filamentous fungi. Fungal Genet. Biol. 2004, 41, 973–981. [Google Scholar] [CrossRef]
- Szewczyk, E.; Nayak, T.; Oakley, C.E.; Edgerton, H.; Xiong, Y.; Taheri-Talesh, N.; Osmani, S.A.; Oakley, B.R. Fusion PCR and gene targeting in Aspergillus nidulans. Nat. Protoc. 2006, 1, 3111–3120. [Google Scholar] [CrossRef] [PubMed]
- Shin, K.S.; Kim, Y.H.; Yu, J.H. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus. Biochem. Biophys. Res. Commun. 2015, 463, 428–433. [Google Scholar] [CrossRef] [PubMed]
- Mah, J.H.; Yu, J.H. Upstream and downstream regulation of asexual development in Aspergillus fumigatus. Eukaryot. Cell 2006, 5, 1585–1595. [Google Scholar] [CrossRef] [Green Version]
- Han, K.H.; Seo, J.A.; Yu, J.H. A putative G protein-coupled receptor negatively controls sexual development in Aspergillus nidulans. Mol. Microbiol. 2004, 51, 1333–1345. [Google Scholar] [CrossRef]
- Song, H.; Dang, X.; He, Y.Q.; Zhang, T.; Wang, H.Y. Selection of housekeeping genes as internal controls for quantitative RT-PCR analysis of the veined rapa whelk (Rapana venosa). PeerJ 2017, 5, e3398. [Google Scholar] [CrossRef] [Green Version]
- Huan, P.; Wang, H.; Liu, B. Assessment of housekeeping genes as internal references in quantitative expression analysis during early development of oyster. Genes Genet. Syst. 2017, 91, 257–265. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2−DDCT Method. Methods 2001, 25, 402–408. [Google Scholar] [CrossRef]
- Choi, Y.H.; Jun, S.C.; Lee, M.W.; Yu, J.H.; Shin, K.S. Characterization of the mbsA Gene Encoding a Putative APSES Transcription Factor in Aspergillus fumigatus. Int. J. Mol. Sci. 2021, 22, 3777. [Google Scholar] [CrossRef]
- Bok, J.W.; Keller, N.P. LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot. Cell 2004, 3, 527–535. [Google Scholar] [CrossRef] [Green Version]
- Wayne, L.G.; Diaz, G.A. A double staining method for differentiating between two classes of mycobacterial catalase in polyacrylamide electrophoresis gels. Anal. Biochem. 1986, 157, 89–92. [Google Scholar] [CrossRef]
- Beauchamp, C.; Fridovich, I. Superoxide dismutase: Improved assays and an assay applicable to acrylamide gels. Anal. Biochem. 1971, 44, 276–287. [Google Scholar] [CrossRef]
- Palmer, J.M.; Keller, N.P. Secondary metabolism in fungi: Does chromosomal location matter? Curr. Opin. Microbiol. 2010, 13, 431–436. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Langmead, B.; Salzberg, S.L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 2012, 9, 357–359. [Google Scholar] [CrossRef] [Green Version]
- Quinlan, A.R.; Hall, I.M. BEDTools: A flexible suite of utilities for comparing genomic features. Bioinformatics 2010, 26, 841–842. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gentleman, R.C.; Carey, V.J.; Bates, D.M.; Bolstad, B.; Dettling, M.; Dudoit, S.; Ellis, B.; Gautier, L.; Ge, Y.; Gentry, J.; et al. Bioconductor: Open software development for computational biology and bioinformatics. Genome Biol. 2004, 5, R80. [Google Scholar] [CrossRef] [Green Version]
- Jun, S.C.; Choi, Y.H.; Lee, M.W.; Yu, J.H.; Shin, K.S. The Putative APSES Transcription Factor RgdA Governs Growth, Development, Toxigenesis, and Virulence in Aspergillus fumigatus. Msphere 2020, 5, e00998-20. [Google Scholar] [CrossRef]
- Stolz, D.J.; Sands, E.M.; Amarsaikhan, N.; Tsoggerel, A.; Templeton, S.P. Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis. J. Vis. Exp. 2018, 133, e57155. [Google Scholar] [CrossRef] [Green Version]
- Sun, Q.; Zhou, D.X. Rice jmjC domain-containing gene JMJ706 encodes H3K9 demethylase required for floral organ development. Proc. Natl. Acad. Sci. USA 2008, 105, 13679–13684. [Google Scholar] [CrossRef] [Green Version]
- Ponnaluri, V.K.; Vavilala, D.T.; Putty, S.; Gutheil, W.G.; Mukherji, M. Identification of non-histone substrates for JMJD2A-C histone demethylases. Biochem. Biophys. Res. Commun. 2009, 390, 280–284. [Google Scholar] [CrossRef]
- Klose, R.J.; Gardner, K.E.; Liang, G.; Erdjument-Bromage, H.; Tempst, P.; Zhang, Y. Demethylation of histone H3K36 and H3K9 by Rph1: A vestige of an H3K9 methylation system in Saccharomyces cerevisiae? Mol. Cell Biol. 2007, 27, 3951–3961. [Google Scholar] [CrossRef] [Green Version]
- Kim, T.; Buratowski, S. Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation. J. Biol. Chem. 2007, 282, 20827–20835. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cloos, P.A.; Christensen, J.; Agger, K.; Maiolica, A.; Rappsilber, J.; Antal, T.; Hansen, K.H.; Helin, K. The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3. Nature 2006, 442, 307–311. [Google Scholar] [CrossRef] [PubMed]
- Chang, Y.; Wu, J.; Tong, X.J.; Zhou, J.Q.; Ding, J. Crystal structure of the catalytic core of Saccharomyces cerevesiae histone demethylase Rph1: Insights into the substrate specificity and catalytic mechanism. Biochem. J. 2011, 433, 295–302. [Google Scholar] [CrossRef] [PubMed]
- Lambou, K.; Lamarre, C.; Beau, R.; Dufour, N.; Latge, J.P. Functional analysis of the superoxide dismutase family in Aspergillus fumigatus. Mol. Microbiol. 2010, 75, 910–923. [Google Scholar] [CrossRef] [PubMed]
- Nakanishi, T.; Sekimizu, K. SDT1/SSM1, a multicopy suppressor of S-II null mutant, encodes a novel pyrimidine 5′-nucleotidase. J. Biol. Chem. 2002, 277, 22103–22106. [Google Scholar] [CrossRef] [Green Version]
- Escobar-Henriques, M.; Daignan-Fornier, B. Transcriptional regulation of the yeast GMP synthesis pathway by its end products. J. Biol. Chem. 2001, 276, 1523–1530. [Google Scholar] [CrossRef] [Green Version]
- Black, J.C.; Van Rechem, C.; Whetstine, J.R. Histone lysine methylation dynamics: Establishment, regulation, and biological impact. Mol. Cell 2012, 48, 491–507. [Google Scholar] [CrossRef] [Green Version]
- South, P.F.; Harmeyer, K.M.; Serratore, N.D.; Briggs, S.D. H3K4 methyltransferase Set1 is involved in maintenance of ergosterol homeostasis and resistance to Brefeldin A. Proc. Natl. Acad. Sci. USA 2013, 110, E1016–E1025. [Google Scholar] [CrossRef] [Green Version]
- Serratore, N.D.; Baker, K.M.; Macadlo, L.A.; Gress, A.R.; Powers, B.L.; Atallah, N.; Westerhouse, K.M.; Hall, M.C.; Weake, V.M.; Briggs, S.D. A Novel Sterol-Signaling Pathway Governs Azole Antifungal Drug Resistance and Hypoxic Gene Repression in Saccharomyces cerevisiae. Genetics 2018, 208, 1037–1055. [Google Scholar] [CrossRef] [Green Version]
- Verweij, P.E.; Te Dorsthorst, D.T.; Janssen, W.H.; Meis, J.F.; Mouton, J.W. In vitro activities at pH 5.0 and pH 7.0 and in vivo efficacy of flucytosine against Aspergillus fumigatus. Antimicrob. Agents Chemother. 2008, 52, 4483–4485. [Google Scholar] [CrossRef] [Green Version]
- Shaw, R.J.; Reines, D. Saccharomyces cerevisiae transcription elongation mutants are defective in PUR5 induction in response to nucleotide depletion. Mol. Cell Biol. 2000, 20, 7427–7437. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nakanishi, T.; Nakano, A.; Nomura, K.; Sekimizu, K.; Natori, S. Purification, gene cloning, and gene disruption of the transcription elongation factor S-II in Saccharomyces cerevisiae. J. Biol. Chem. 1992, 267, 13200–13204. [Google Scholar] [CrossRef]
- Exinger, F.; Lacroute, F. 6-Azauracil inhibition of GTP biosynthesis in Saccharomyces cerevisiae. Curr. Genet. 1992, 22, 9–11. [Google Scholar] [CrossRef] [PubMed]
- Li, B.; Howe, L.; Anderson, S.; Yates, J.R., 3rd; Workman, J.L. The Set2 histone methyltransferase functions through the phosphorylated carboxyl-terminal domain of RNA polymerase II. J. Biol. Chem. 2003, 278, 8897–8903. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Krogan, N.J.; Kim, M.; Tong, A.; Golshani, A.; Cagney, G.; Canadien, V.; Richards, D.P.; Beattie, B.K.; Emili, A.; Boone, C.; et al. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol. Cell Biol. 2003, 23, 4207–4218. [Google Scholar] [CrossRef] [Green Version]
- De Castro, P.A.; Colabardini, A.C.; Moraes, M.; Horta, M.A.C.; Knowles, S.L.; Raja, H.A.; Oberlies, N.H.; Koyama, Y.; Ogawa, M.; Gomi, K.; et al. Regulation of gliotoxin biosynthesis and protection in Aspergillus species. PLoS Genet. 2022, 18, e1009965. [Google Scholar] [CrossRef]
Strain | Genotype | Reference |
---|---|---|
A. nidulans FGSC4 | veA+ (Wild type) | FGSC a |
Af293 | Wild type | [16] |
Af293.1 | pyrG1 | [19] |
ΔkdmA | ΔkdmA::AnipyrG; AfupyrG1 | This study |
ΔkdmB | ΔkdmB::AnipyrG; AfupyrG1 | This study |
C’ kdmA | ΔkdmA::AnipyrG; AfupyrG1; kdmA::hygB | This study |
C’ kdmB | ΔkdmB::AnipyrG; AfupyrG1; kdmB::hygB | This study |
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Choi, Y.-H.; Lee, M.-W.; Shin, K.-S. The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in Aspergillus fumigatus. J. Fungi 2022, 8, 590. https://doi.org/10.3390/jof8060590
Choi Y-H, Lee M-W, Shin K-S. The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in Aspergillus fumigatus. Journal of Fungi. 2022; 8(6):590. https://doi.org/10.3390/jof8060590
Chicago/Turabian StyleChoi, Yong-Ho, Min-Woo Lee, and Kwang-Soo Shin. 2022. "The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in Aspergillus fumigatus" Journal of Fungi 8, no. 6: 590. https://doi.org/10.3390/jof8060590