Skip to main content
SpringerLink
Log in

Conservation and diversity of the regulators of cellulolytic enzyme genes in Ascomycete fungi

  • Review
  • Published:
Current Genetics Aims and scope Submit manuscript

Abstract

In the past decade, various transcriptional activators of cellulolytic enzyme genes have been identified in Ascomycete fungi. The regulatory system of cellulolytic enzymes is not only partially conserved, but also significantly diverse. For example, Trichoderma reesei has a system distinct from those of Aspergillus and Neurospora crassa—the former utilizes Xyr1 (the Aspergillus XlnR ortholog) as the major regulator of cellulolytic enzyme genes, while the latter uses CLR-2/ClrB/ManR orthologs. XlnR/Xyr1 and CLR-2/ClrB/ManR are evolutionarily distant from each other. Regulatory mechanisms that are controlled by CLR-2, ClrB, and ManR are also significantly different, although they are orthologous factors. Expression of clr-2 requires the activation of another transcription factor, CLR-1, by cellobiose, while CLR-2 is constitutively active for transactivation. By contrast, ClrB activation requires cellobiose. While ClrB mainly regulates cellulolytic genes, ManR is essential for the activation of not only cellulolytic but also mannanolytic enzyme genes. In this review, we summarize XlnR/Xyr1- and CLR-2/ClrB/ManR-dependent regulation in N. crassa, A. nidulans, A. oryzae, and T. reesei and emphasize the conservation and diversity of the regulatory systems for cellulolytic enzyme genes in these Ascomycete fungi. In addition, we discuss the role of McmA, another transcription factor that plays an important role in recruiting ClrB to the promoters in A. nidulans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Alam MA, Kelly JM (2016) Proteins interacting with CreA and CreB in the carbon catabolite repression network in Aspergillus nidulans. Curr Genet. doi:10.1007/s00294-016-0667-2

    Google Scholar 

  • Alam MA, Kamlangdee N, Kelly JM (2016) The CreB deubiquitinating enzyme does not directly target the CreA repressor protein in Aspergillus nidulans. Curr Genet. doi:10.1007/s00294-016-0666-3

    Google Scholar 

  • Aro N, Saloheimo A, Ilmén M, Penttilä M (2001) ACEII, a novel transcriptional activator involved in regulation of cellulase and xylanase genes of Trichoderma reesei. J Biol Chem 276:24309–24314. doi:10.1074/jbc.M003624200

    Article  CAS  PubMed  Google Scholar 

  • Battaglia E, Klaubauf S, Vallet J, Ribot C, Lebrun MH, de Vries RP (2013) Xlr1 is involved in the transcriptional control of the pentose catabolic pathway, but not hemi-cellulolytic enzymes in Magnaporthe oryzae. Fungal Genet Biol 57:76–84. doi:10.1016/j.fgb.2013.06.005

    Article  CAS  PubMed  Google Scholar 

  • Bernreiter A, Ramon A, Fernández-Martinez J, Berger H, Araújo-Bazan L, Espeso EA, Pachlinger R, Gallmetzer A, Ander I, Scazzocchio C, Strauss J (2007) Nuclear export of the transcription factor NirA is a regulatory checkpoint for nitrate induction in Aspergillus nidulans. Mol Cell Biol 27:791–802. doi:10.1128/Mcb.00761-06

    Article  CAS  PubMed  Google Scholar 

  • Bhat PJ, Iyer RS (2009) Epigenetics of the yeast galactose genetic switch. J Biosci 34:513–522

    Article  CAS  PubMed  Google Scholar 

  • Brunner K, Lichtenauer AM, Kratochwill K, Delic M, Mach RL (2007) Xyr1 regulates xylanase but not cellulase formation in the head blight fungus Fusarium graminearum. Curr Genet 52:213–220. doi:10.1007/s00294-007-0154-x

    Article  CAS  PubMed  Google Scholar 

  • Campos Antoniêto AC, Ramos Pedersoli W, Dos Santos Castro L, da Silva Santos R, Cruz AH, Nogueira KM, Silva-Rocha R, Rossi A, Silva RN (2017) Deletion of pH regulator pac-3 affects cellulase and xylanase activity during sugarcane bagasse degradation by Neurospora crassa. PLoS ONE 12:e0169796. doi:10.1371/journal.pone.0169796

    Article  PubMed  PubMed Central  Google Scholar 

  • Coradetti ST, Craig JP, Xiong Y, Shock T, Tian C, Glass NL (2012) Conserved and essential transcription factors for cellulase gene expression in Ascomycete fungi. Proc Natl Acad Sci USA 109:7397–7402. doi:10.1073/pnas.1200785109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coradetti ST, Xiong Y, Glass NL (2013) Analysis of a conserved cellulase transcriptional regulator reveals inducer-independent production of cellulolytic enzymes in Neurospora crassa. Microbiologyopen 2:595–609. doi:10.1002/mbo3.94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Craig JP, Coradetti ST, Starr TL, Glass NL (2015) Direct target network of the Neurospora crassa plant cell wall deconstruction regulators CLR-1, CLR-2, and XLR-1. MBio. doi:10.1128/mBio.01452-15

    PubMed  PubMed Central  Google Scholar 

  • Dos Reis TF, de Lima PB, Parachin NS, Mingossi FB, de Castro Oliveira JV, Ries LN, Goldman GH (2016) Identification and characterization of putative xylose and cellobiose transporters in Aspergillus nidulans. Biotechnol Biofuels 9:204. doi:10.1186/s13068-016-0611-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Dowzer CEA, Kelly JM (1991) Analysis of the creA gene, a regulator of carbon catabolite repression in Aspergillus nidulans. Mol Cell Biol 11:5701–5709. doi:10.1128/MCB.11.11.5701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Endo Y, Yokoyama M, Morimoto M, Shirai K, Chikamatsu G, Kato N, Tsukagoshi N, Kato M, Kobayashi T (2008) Novel promoter sequence required for inductive expression of the Aspergillus nidulans endoglucanase gene eglA. Biosci Biotechnol Biochem 72:312–320. doi:10.1271/bbb.70278

    Article  CAS  PubMed  Google Scholar 

  • Furukawa T, Shida Y, Kitagami N, Mori K, Kato M, Kobayashi T, Okada H, Ogasawara W, Morikawa Y (2009) Identification of specific binding sites for XYR1, a transcriptional activator of cellulolytic and xylanolytic genes in Trichoderma reesei. Fungal Genet Biol 46:564–574. doi:10.1016/j.fgb.2009.04.001

    Article  CAS  PubMed  Google Scholar 

  • Gielkens MMC, Dekkers E, Visser J, de Graaff LH (1999) Two cellobiohydrolase-encoding genes from Aspergillus niger require D-xylose and the xylanolytic transcriptional activator XlnR for their expression. Appl Environ Microbiol 65:4340–4345

    CAS  PubMed  PubMed Central  Google Scholar 

  • Häkkinen M, Valkonen MJ, Westerholm-Parvinen A, Aro N, Arvas M, Vitikainen M, Penttilä M, Saloheimo M, Pakula TM (2014) Screening of candidate regulators for cellulase and hemicellulase production in Trichoderma reesei and identification of a factor essential for cellulase production. Biotechnol Biofuels 7:14. doi:10.1186/1754-6834-7-14

    Article  PubMed  PubMed Central  Google Scholar 

  • Häkkinen M, Sivasiddarthan D, Aro N, Saloheimo M, Pakula TM (2015) The effects of extracellular pH and of the transcriptional regulator PACI on the transcriptome of Trichoderma reesei. Microb Cell Fact 14:63. doi:10.1186/s12934-015-0247-z

    Article  PubMed  PubMed Central  Google Scholar 

  • Hasper AA, Trindade LM, van der Veen D, van Ooyen AJ, de Graaff LH (2004) Functional analysis of the transcriptional activator XlnR from Aspergillus niger. Microbiology 150:1367–1375. doi:10.1099/mic.0.26557-0

    Article  CAS  PubMed  Google Scholar 

  • He R, Ma L, Li C, Jia W, Li D, Zhang D, Chen S (2014) Trpac1, a pH response transcription regulator, is involved in cellulase gene expression in Trichoderma reesei. Enzyme Microb Technol 67:17–26. doi:10.1016/j.enzmictec.2014.08.013

    Article  CAS  PubMed  Google Scholar 

  • Huberman LB, Liu J, Qin L, Glass NL (2016) Regulation of the lignocellulolytic response in filamentous fungi. Fungal Biol Rev 30:101–111. doi:10.1016/j.fbr.2016.06.001

    Article  Google Scholar 

  • Iyer D, Chang D, Marx J, Wei L, Olson EN, Parmacek MS, Balasubramanyam A, Schwartz RJ (2006) Serum response factor MADS box serine-162 phosphorylation switches proliferation and myogenic gene programs. Proc Natl Acad Sci USA 103:4516–4521. doi:10.1073/pnas.0505338103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klaubauf S, Narang HM, Post H, Zhou M, Brunner K, Mach-Aigner AR, Mach RL, Heck AJ, Altelaar AF, de Vries RP (2014) Similar is not the same: differences in the function of the (hemi-)cellulolytic regulator XlnR (Xlr1/Xyr1) in filamentous fungi. Fungal Genet Biol 72:73–81. doi:10.1016/j.fgb.2014.07.007

    Article  CAS  PubMed  Google Scholar 

  • Kojima T, Kunitake E, Ihara K, Kobayashi T, Nakano H (2016) A robust analytical pipeline for genome-wide identification of the genes regulated by a transcription factor: combinatorial analysis performed using gSELEX-Seq and RNA-Seq. PLoS ONE 11:e0159011. doi:10.1371/journal.pone.0159011

    Article  PubMed  PubMed Central  Google Scholar 

  • Kunitake E, Tani S, Sumitani J, Kawaguchi T (2013) A novel transcriptional regulator, ClbR, controls the cellobiose- and cellulose-responsive induction of cellulase and xylanase genes regulated by two distinct signaling pathways in Aspergillus aculeatus. Appl Microbiol Biotechnol 97:2017–2028. doi:10.1007/s00253-012-4305-8

    Article  CAS  PubMed  Google Scholar 

  • Kunitake E, Kawamura A, Tani S, Takenaka S, Ogasawara W, Sumitani J, Kawaguchi T (2015) Effects of clbR overexpression on enzyme production in Aspergillus aculeatus vary depending on the cellulosic biomass-degrading enzyme species. Biosci Biotechnol Biochem 79:488–495. doi:10.1080/09168451.2014.982501

    Article  CAS  PubMed  Google Scholar 

  • Kunitake E, Hagiwara D, Miyamoto K, Kanamaru K, Kimura M, Kobayashi T (2016) Regulation of genes encoding cellulolytic enzymes by Pal-PacC signaling in Aspergillus nidulans. Appl Microbiol Biotechnol 100:3621–3635. doi:10.1007/s00253-016-7409-8

    Article  CAS  PubMed  Google Scholar 

  • Kuo MH, Nadeau ET, Grayhack EJ (1997) Multiple phosphorylated forms of the Saccharomyces cerevisiae Mcm1 protein include an isoform induced in response to high salt concentrations. Mol Cell Biol 17:819–832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lan C, Lee HC, Tang S, Zhang L (2004) A novel mode of chaperone action: heme activation of Hap1 by enhanced association of Hsp90 with the repressed Hsp70-Hap1 complex. J Biol Chem 279:27607–27612. doi:10.1074/jbc.M402777200

    Article  CAS  PubMed  Google Scholar 

  • Lei Y, Liu G, Yao G, Li Z, Qin Y, Qu Y (2016) A novel bZIP transcription factor ClrC positively regulates multiple stress responses, conidiation and cellulase expression in Penicillium oxalicum. Res Microbiol 167:424–435. doi:10.1016/j.resmic.2016.03.001

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Yao G, Wu R, Gao L, Kan Q, Liu M, Yang P, Liu G, Qin Y, Song X, Zhong Y, Fang X, Qu Y (2015) Synergistic and dose-controlled regulation of cellulase gene expression in Penicillium oxalicum. PLoS Genet 11:e1005509. doi:10.1371/journal.pgen.1005509

    Article  PubMed  PubMed Central  Google Scholar 

  • Li N, Kunitake E, Aoyama M, Ogawa M, Kanamaru K, Kimura M, Koyama Y, Kobayashi T (2016a) McmA-dependent and -independent regulatory systems governing expression of ClrB-regulated cellulase and hemicellulase genes in Aspergillus nidulans. Mol Microbiol 102:810–826. doi:10.1111/mmi.13493

    Article  CAS  PubMed  Google Scholar 

  • Li N, Kunitake E, Endo Y, Aoyama M, Kanamaru K, Kimura M, Kato M, Kobayashi T (2016b) Involvement of an SRF-MADS protein McmA in regulation of extracellular enzyme production and asexual/sexual development in Aspergillus nidulans. Biosci Biotechnol Biochem 80:1820–1828. doi:10.1080/09168451.2016.1146074

    Article  CAS  PubMed  Google Scholar 

  • Lockington RA, Kelly JM (2002) The WD-40-repeat protein CreC interacts with and stabilizes the deubiquitinating enzyme CreB in vivo in Aspergillus nidulans. Mol Microbiol 43:1173–1182. doi:10.1046/j.1365-2958.2002.02811.x

    Article  CAS  PubMed  Google Scholar 

  • Ma L, Chen L, Zhang L, Zou G, Liu R, Jiang Y, Zhou Z (2016) RNA sequencing reveals Xyr1 as a transcription factor regulating gene expression beyond carbohydrate metabolism. Biomed Res Int 2016:4841756. doi:10.1155/2016/4841756

    PubMed  PubMed Central  Google Scholar 

  • Makita T, Katsuyama Y, Tani S, Suzuki H, Kato N, Todd RB, Hynes MJ, Tsukagoshi N, Kato M, Kobayashi T (2009) Inducer-dependent nuclear localization of a Zn(II)(2)Cys(6) transcriptional activator, AmyR, in Aspergillus nidulans. Biosci Biotechnol Biochem 73:391–399. doi:10.1271/bbb.80654

    Article  CAS  PubMed  Google Scholar 

  • Marui J, Kitamoto N, Kato M, Kobayashi T, Tsukagoshi N (2002a) Transcriptional activator, AoXlnR, mediates cellulose-inductive expression of the xylanolytic and cellulolytic genes in Aspergillus oryzae. FEBS Lett 528:279–282

    Article  CAS  PubMed  Google Scholar 

  • Marui J, Tanaka A, Mimura S, de Graaff LH, Visser J, Kitamoto N, Kato M, Kobayashi T, Tsukagoshi N (2002b) A transcriptional activator, AoXlnR, controls the expression of genes encoding xylanolytic enzymes in Aspergillus oryzae. Fungal Genet Biol 35:157–169. doi:10.1006/fgbi.2001.1321

    Article  CAS  PubMed  Google Scholar 

  • Messenguy F, Dubois E (2003) Role of MADS box proteins and their cofactors in combinatorial control of gene expression and cell development. Gene 316:1–21

    Article  CAS  PubMed  Google Scholar 

  • Murakoshi Y, Makita T, Kato M, Kobayashi T (2012) Comparison and characterization of α-amylase inducers in Aspergillus nidulans based on nuclear localization of AmyR. Appl Microbiol Biotechnol 94:1629–1635. doi:10.1007/s00253-012-3874-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Noguchi Y, Sano M, Kanamaru K, Ko T, Takeuchi M, Kato M, Kobayashi T (2009) Genes regulated by AoXlnR, the xylanolytic and cellulolytic transcriptional regulator, in Aspergillus oryzae. Appl Microbiol Biotechnol 85:141–154. doi:10.1007/s00253-009-2236-9

    Article  CAS  PubMed  Google Scholar 

  • Noguchi Y, Tanaka H, Kanamaru K, Kato M, Kobayashi T (2011) Xylose triggers reversible phosphorylation of XlnR, the fungal transcriptional activator of xylanolytic and cellulolytic genes in Aspergillus oryzae. Biosci Biotechnol Biochem 75:953–959. doi:10.1271/bbb.100923

    Article  CAS  PubMed  Google Scholar 

  • Ogawa M, Kobayashi T, Koyama Y (2012) ManR, a novel Zn(II)2Cys6 transcriptional activator, controls the β-mannan utilization system in Aspergillus oryzae. Fungal Genet Biol 49:987–995. doi:10.1016/j.fgb.2012.09.006

    Article  CAS  PubMed  Google Scholar 

  • Ogawa M, Kobayashi T, Koyama Y (2013) ManR, a transcriptional regulator of the β-mannan utilization system, controls the cellulose utilization system in Aspergillus oryzae. Biosci Biotechnol Biochem 77:426–429. doi:10.1271/bbb.120795

    Article  CAS  PubMed  Google Scholar 

  • Ries LNA, Beattie SR, Espeso EA, Cramer RA, Goldman GH (2016) Diverse regulation of the CreA carbon catabolite repressor in Aspergillus nidulans. Genetics 203:335–352. doi:10.1534/genetics.116.187872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sella L, Gazzetti K, Castiglioni C, Schäfer W, D’Ovidio R, Favaron F (2016) The Fusarium graminearum Xyr1 transcription factor regulates xylanase expression but is not essential for fungal virulence. Plant Pathol 65:713–722. doi:10.1111/ppa.12456

    Article  CAS  Google Scholar 

  • Sellick CA, Reece RJ (2003) Modulation of transcription factor function by an amino acid: activation of Put3p by proline. EMBO J 22:5147–5153. doi:10.1093/emboj/cdg480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stricker AR, Grosstessner-Hain K, Würleitner E, Mach RL (2006) Xyr1 (xylanase regulator 1) regulates both the hydrolytic enzyme system and D-xylose metabolism in Hypocrea jecorina. Eukaryot Cell 5:2128–2137. doi:10.1128/EC.00211-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun J, Tian C, Diamond S, Glass NL (2012) Deciphering transcriptional regulatory mechanisms associated with hemicellulose degradation in Neurospora crassa. Eukaryot Cell 11:482–493. doi:10.1128/EC.05327-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka A, Kamei K, Tanoue S, Papagiannopoulos P, Steidl S, Brakhage AA, Davis MA, Hynes MJ, Kato M, Kobayashi T, Tsukagoshi N (2001) AoHapB, AoHapC and AoHapE, subunits of the Aspergillus oryzae CCAAT-binding complex, are functionally interchangeable with the corresponding subunits in Aspergillus nidulans. Curr Genet 39:175–182

    Article  CAS  PubMed  Google Scholar 

  • Tani S, Kawaguchi T, Kobayashi T (2014) Complex regulation of hydrolytic enzyme genes for cellulosic biomass degradation in filamentous fungi. Appl Microbiol Biotechnol 98:4829–4837. doi:10.1007/s00253-014-5707-6

    Article  CAS  PubMed  Google Scholar 

  • van Peij NN, Gielkens MM, de Vries RP, Visser J, de Graaff LH (1998) The transcriptional activator XlnR regulates both xylanolytic and endoglucanase gene expression in Aspergillus niger. Appl Environ Microbiol 64:3615–3619

    PubMed  PubMed Central  Google Scholar 

  • Wang D, Zheng F, Holmberg S, Kohlhaw GB (1999) Yeast transcriptional regulator Leu3. Self-masking, specificity of masking, and evidence for regulation by the intracellular level of Leu3p. J Biol Chem 274:19017–19024

    Article  CAS  PubMed  Google Scholar 

  • Yamakawa Y, Endo Y, Li N, Yoshizawa M, Aoyama M, Watanabe A, Kanamaru K, Kato M, Kobayashi T (2013) Regulation of cellulolytic genes by McmA, the SRF-MADS box protein in Aspergillus nidulans. Biochem Biophys Res Commun 431:777–782. doi:10.1016/j.bbrc.2013.01.031

    Article  CAS  PubMed  Google Scholar 

  • Zeilinger S, Ebner A, Marosits T, Mach R, Kubicek CP (2001) The Hypocrea jecorina HAP 2/3/5 protein complex binds to the inverted CCAAT-box (ATTGG) within the cbh2 (cellobiohydrolase II-gene) activating element. Mol Genet Genom 266:56–63

    Article  CAS  Google Scholar 

  • Znameroski EA, Li X, Tsai JC, Galazka JM, Glass NL, Cate JH (2014) Evidence for transceptor function of cellodextrin transporters in Neurospora crassa. J Biol Chem 289:2610–2619. doi:10.1074/jbc.M113.533273

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Works on A. oryzae XlnR and A. nidulans ClrB and McmA in Nagoya University were partially supported by the Program for Promotion of Basic and Applied Research for Innovations in Bio-oriented Industry, and by the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries, and Food Industry to T.K.

Author information

Authors and Affiliations

  1. Laboratory of Applied Microbiology, Department of Biological Mechanisms and Functions, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan

    Emi Kunitake & Tetsuo Kobayashi

  2. Microbial Genetics Laboratory, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya-cho, Tsu, 514-8507, Japan

    Emi Kunitake

Authors
  1. Emi Kunitake
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tetsuo Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tetsuo Kobayashi.

Additional information

Communicated by M. Kupiec.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kunitake, E., Kobayashi, T. Conservation and diversity of the regulators of cellulolytic enzyme genes in Ascomycete fungi. Curr Genet 63, 951–958 (2017). https://doi.org/10.1007/s00294-017-0695-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00294-017-0695-6

Keywords

Search

Navigation