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The putative C2H2 transcription factor RocA is a novel regulator of development and secondary metabolism in Aspergillus nidulans

  • Microbial Genetics, Genomics and Molecular Biology
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Abstract

Multiple transcriptional regulators play important roles in the coordination of developmental processes, including asexual and sexual development, and secondary metabolism in the filamentous fungus Aspergillus nidulans. In the present study, we characterized a novel putative C2H2-type transcription factor (TF), RocA, in relation to development and secondary metabolism. Deletion of rocA increased conidiation and caused defective sexual development. In contrast, the overexpression of rocA exerted opposite effects on both phenotypes. Additionally, nullifying rocA resulted in enhanced brlA expression and reduced nsdC expression, whereas its overexpression exerted the opposite effects. These results suggest that RocA functions as a negative regulator of asexual development by repressing the expression of brlA encoding a key asexual development activator, but as a positive regulator of sexual development by enhancing the expression of nsdC encoding a pivotal sexual development activator. Deletion of rocA increased the production of sterigmatocystin (ST), as well as the expression of its biosynthetic genes, aflR and stcU. Additionally, the expression of the biosynthetic genes for penicillin (PN), ipnA and acvA, and for terrequinone (TQ), tdiB and tdiE, was increased by rocA deletion. Thus, it appears that RocA functions as a negative transcriptional modulator of the secondary metabolic genes involved in ST, PN, and TQ biosynthesis. Taken together, we propose that RocA is a novel transcriptional regulator that may act either positively or negatively at multiple target genes necessary for asexual and sexual development and secondary metabolism.

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References

  • Adams, T.H., Boylan, M.T., and Timberlake, W.E. 1988. brlA is necessary and sufficient to direct conidiophore development in Aspergillus nidulans. Cell54, 353–362.

    Article  CAS  PubMed  Google Scholar 

  • Adams, T.H., Deising, H., and Timberlake, W.E. 1990. brlA requires both zinc fingers to induce development. Mol. Cell Biol.10, 1815–1817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adams, T.H., Wieser, J.K., and Yu, J.H. 1998. Asexual sporulation in Aspergillus nidulans. Microbiol. Mol. Biol. Rev.62, 35–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahmed, Y.L., Gerke, J., Park, H.S., Bayram, Ö., Neumann, P., Ni, M., Dickmanns, A., Kim, S.C., Yu, J.H., Braus, G.H., et al. 2013. The velvet family of fungal regulators contains a DNA-binding domain structurally similar to NF-κB. PLoS Biol.11, e1001750.

    Article  PubMed  PubMed Central  Google Scholar 

  • Aramayo, R. and Timberlake, W.E. 1993. The Aspergillus nidulans yA gene is regulated by abaA. EMBO J.12, 2039–2048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bayram, O. and Braus, G.H. 2012. Coordination of secondary metabolism and development in fungi: the velvet family of regulatory proteins. FEMS Microbiol. Rev.36, 1–24.

    Article  CAS  PubMed  Google Scholar 

  • Bayram, O., Krappmann, S., Ni, M., Bok, J.W., Helmstaedt, K., Valerius, O., Braus-Stromeyer, S., Kwon, N.J., Keller, N.P., Yu, J.H., et al. 2008. VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science320, 1504–1506.

    Article  CAS  PubMed  Google Scholar 

  • Bok, J.W. and Keller, N.P. 2004. LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot. Cell3, 527–535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borneman, A.R., Hynes, M.J., and Andrianopoulos, A. 2001. An STE12 homolog from the asexual, dimorphic fungus Penicillium marneffei complements the defect in sexual development of an Aspergillus nidulans steA mutant. Genetics157, 1003–1014.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bouhired, S., Weber, M., Kempf-Sontag, A., Keller, N.P., and Hoffmeister, D. 2007. Accurate prediction of the Aspergillus nidulans terrequinone gene cluster boundaries using the transcriptional regulator LaeA. Fungal Genet. Biol.44, 1134–1145.

    Article  CAS  PubMed  Google Scholar 

  • Boylan, M.T., Mirabito, P.M., Willett, C.E., Zimmerman, C.R., and Timberlake, W.E. 1987. Isolation and physical characterization of three essential conidiation genes from Aspergillus nidulans. Mol. Cell Biol.7, 3113–3118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calvo, A.M., Wilson, R.A., Bok, J.W., and Keller, N.P. 2002. Relationship between secondary metabolism and fungal development. Microbiol. Mol. Biol. Rev.66, 447–459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, Y., Leal, A.D., Patel, S., and Gorski, D.H. 2007. The homeobox gene GAX activates p21WAF1/CIP1 expression in vascular endothelial cells through direct interaction with upstream AT-rich sequences. J. Biol. Chem.282, 507–517.

    Article  CAS  PubMed  Google Scholar 

  • Douville, J.M., Cheung, D.Y., Herbert, K.L., Moffatt, T., and Wigle, J.T. 2011. Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21CIP1/WAF1 and p16INK4a in vascular endothelial cells. PLoS One6, e29099.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dyer, P.S. and O’Gorman, C.M. 2012. Sexual development and cryptic sexuality in fungi: insights from Aspergillus species. FEMS Microbiol. Rev.36, 165–192.

    Article  CAS  PubMed  Google Scholar 

  • Fernandes, M., Keller, N.P., and Adams, T.H. 1998. Sequence-specific binding by Aspergillus nidulans AflR, a C6 zinc cluster protein regulating mycotoxin biosynthesis. Mol. Microbiol.28, 1355–1365.

    Article  CAS  PubMed  Google Scholar 

  • Han, K.H. 2009. Molecular genetics of Emericella nidulans sexual development. Mycobiology37, 171–182.

    Article  PubMed  PubMed Central  Google Scholar 

  • Han, K.H., Han, K.Y., Yu, J.H., Chae, K.S., Jahng, K.Y., and Han, D.M. 2001. The nsdD gene encodes a putative GATA-type transcription factor necessary for sexual development of Aspergillus nidulans. Mol. Microbiol.41, 299–309.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H.R., Chae, K.S., Han, K.H., and Han, D.M. 2009. The nsdC gene encoding a putative C2H2-type transcription factor is a key activator of sexual development in Aspergillus nidulans. Genetics182, 771–783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, H., Han, K., Kim, K., Han, D., Jahng, K., and Chae, K. 2002. The veA gene activates sexual development in Aspergillus nidulans. Fungal Genet. Biol.37, 72–80.

    Article  CAS  PubMed  Google Scholar 

  • Kim, Y.J., Yu, Y.M., and Maeng, P.J. 2017. Differential control of asexual development and sterigmatocystin biosynthesis by a novel regulator in Aspergillus nidulans. Sci. Rep.7, 46340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kwon, N.J., Garzia, A., Espeso, E.A., Ugalde, U., and Yu, J.H. 2010. FlbC is a putative nuclear C2H2 transcription factor regulating development in Aspergillus nidulans. Mol. Microbiol.77, 1203–1219.

    Article  CAS  PubMed  Google Scholar 

  • Lee, B.N. and Adams, T.H. 1996. fluG and flbA function interdependently to initiate conidiophore development in Aspergillus nidulans through brlAβ activation. EMBO J.15, 299–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, M.K., Kwon, N.J., Choi, J.M., Lee, I.S., Jung, S., and Yu, J.H. 2014. NsdD is a key repressor of asexual development in Aspergillus nidulans. Genetics197, 159–173.

    Article  PubMed  PubMed Central  Google Scholar 

  • Marshall, M.A. and Timberlake, W.E. 1991. Aspergillus nidulans wetA activates spore-specific gene expression. Mol. Cell Biol.11, 55–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen Ba, A.N., Pogoutse, A., Provart, N., and Moses, A.M. 2009. NLStradamus: a simple hidden markov model for nuclear localization signal prediction. BMC Bioinformatics10, 202.

    Article  PubMed  PubMed Central  Google Scholar 

  • Paraguison, R.C., Higaki, K., Sakamoto, Y., Hashimoto, O., Miyake, N., Matsumoto, H., Yamamoto, K., Sasaki, T., Kato, N., and Nanba, E. 2005. Polyhistidine tract expansions in HOXA1 result in intranuclear aggregation and increased cell death. Biochem. Biophys. Res. Commun.336, 1033–1039.

    Article  CAS  PubMed  Google Scholar 

  • Park, H.S., Nam, T.Y., Han, K.H., Kim, S.C., and Yu, J.H. 2014. VelC positively controls sexual development in Aspergillus nidulans. PLoS One9, e89883.

    Article  PubMed  PubMed Central  Google Scholar 

  • Park, D.S., Yu, Y.M., Kim, Y.J., and Maeng, P.J. 2015. Negative regulation of the vacuole-mediated resistance to K+ stress by a novel C2H2 zinc finger transcription factor encoded by aslA in Aspergillus nidulans. J. Microbiol.53, 100–110.

    Article  CAS  PubMed  Google Scholar 

  • Ramamoorthy, V., Dhingra, S., Kincaid, A., Shantappa, S., Feng, X., and Calvo, A.M. 2013. The putative C2H2 transcription factor MtfA is a novel regulator of secondary metabolism and morphogenesis in Aspergillus nidulans. PLoS One8, e74122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sambrook, J. and Russell, D.W. 2001. Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory Press, New York, USA.

    Google Scholar 

  • Seo, J.A., Guan, Y., and Yu, J.H. 2003. Suppressor mutations bypass the requirement of fluG for asexual sporulation and sterigmatocystin production in Aspergillus nidulans. Genetics165, 1083–1093.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Seo, J.A., Guan, Y., and Yu, J.H. 2006. FluG-dependent asexual development in Aspergillus nidulans occurs via derepression. Genetics172, 1535–1544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yelton, M.M., Hamer, J.E., and Timberlake, W.E. 1984. Transformation of Aspergillus nidulans by using a trpC plasmid. Proc. Natl. Acad. Sci. USA81, 1470–1474.

    Article  CAS  PubMed  Google Scholar 

  • Yu, Y.M. 2015. Genome-wide analysis reveals the transcriptional programs on the whole process from germination to differentiation in Aspergillus nidulans. Ph. D. thesis. Chungnam National University, Daejeon, Korea.

    Google Scholar 

  • Yu, J.H., Hamari, Z., Han, K.H., Seo, J.A., Reyes-Dominguez, Y., and Scazzocchio, C. 2004. Double-joint PCR: a PCR-based molecular tool for gene manipulations in filamentous fungi. Fungal Genet. Biol.41, 973–981.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the grants from the NRF of Korea, NRF-2018R1D1A1B07043688 and 2017R1A6A3A-01076516.

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  1. Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, Republic of Korea

    Dong Chan Won, Yong Jin Kim, Da Hye Kim, Hee-Moon Park & Pil Jae Maeng

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  1. Dong Chan Won
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  2. Yong Jin Kim
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  3. Da Hye Kim
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Correspondence to Hee-Moon Park or Pil Jae Maeng.

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Won, D.C., Kim, Y.J., Kim, D.H. et al. The putative C2H2 transcription factor RocA is a novel regulator of development and secondary metabolism in Aspergillus nidulans. J Microbiol. 58, 574–587 (2020). https://doi.org/10.1007/s12275-020-0083-7

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