Skip to main content
Log in

Trichoderma reesei Histone Acetyltransferase Gcn5 Regulates Fungal Growth, Conidiation, and Cellulase Gene Expression

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

Gcn5 is a well-established histone acetyltransferase involved in chromatin modification by catalyzing the acetylation of specific lysine residues within the N-terminal tails of the core histones. To assess the role of chromatin remodeling in the transcriptional response of cellulolytic Trichoderma reesei to the changes of environmental conditions, we identified the T. reesei ortholog of Saccharomyces cerevisiae Gcn5 by sequence alignment and functional analysis. Heterologous expression of TrGcn5 in S. cerevisiae gcn5Δ strain restored the growth defect under nutrient limitation as well as stresses. In contrast, mutant TrGcn5 with site-directed changes of residues critical for Gcn5 histone acetyltransferase activity could not complement the growth defect. The T. reesei gcn5Δ mutant strain displayed a strongly decreased growth rate and dramatic morphological changes including misshapen hyphal cells and abolished conidiation. Moreover, the induced expression of cellulase genes was severely impaired in the gcn5Δ T. reesei with acetylation of K9 and K14 of histone H3 in the cellulase gene promoter dramatically affected in the absence of TrGcn5. The results indicate that TrGcn5 plays a critical role in filamentous growth, morphogenesis, and transcriptional activation of specific genes including cellulase encoding genes.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Abrahao-Neto J, Rossini CH, el-Gogary S, Henrique-Silva F, Crivellaro O, el-Dorry H (1995) Mitochondrial functions mediate cellulase gene expression in Trichoderma reesei. Biochemistry (Mosc) 34(33):10456–10462

    Article  CAS  Google Scholar 

  2. Baker SP, Grant PA (2007) The SAGA continues: expanding the cellular role of a transcriptional co-activator complex. Oncogene 26(37):5329–5340

    Article  PubMed  CAS  Google Scholar 

  3. Brenna A, Grimaldi B, Filetici P, Ballario P (2012) Physical association of the WC-1 photoreceptor and the histone acetyltransferase NGF-1 is required for blue light signal transduction in Neurospora crassa. Mol Biol Cell 23(19):3863–3872

    Article  PubMed  CAS  Google Scholar 

  4. Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD (1996) Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84(6):843–851

    Article  PubMed  CAS  Google Scholar 

  5. Brunner K, Omann M, Pucher ME, Delic M, Lehner SM, Domnanich P, Kratochwill K, Druzhinina I, Denk D, Zeilinger S (2008) Trichoderma G protein-coupled receptors: functional characterisation of a cAMP receptor-like protein from Trichoderma atroviride. Curr Genet 54(6):283–299

    Article  PubMed  CAS  Google Scholar 

  6. Burgess RJ, Zhang Z (2010) Roles for Gcn5 in promoting nucleosome assembly and maintaining genome integrity. Cell Cycle 9(15):2979–2985

    Article  PubMed  CAS  Google Scholar 

  7. Carraro DM, Jr Ferreira JR, Schumacher R, Pereira GG, Hollenberg CP, El-Dorry H (1998) A region of the cellobiohydrolase I promoter from the filamentous fungus Trichoderma reesei mediates glucose repression in Saccharomyces cerevisiae, dependent on mitochondrial activity. Biochem Biophys Res Commun 253(2):407–414

    Article  PubMed  CAS  Google Scholar 

  8. Csordas A (1990) On the biological role of histone acetylation. Biochem J 265(1):23–38

    PubMed  CAS  Google Scholar 

  9. David S, Gabriel RM (1982) β-Glucosidase induction and repression in the cellulolytic fungus, Trichoderma reesei. Exp Mycol 6(2):115–124

    Article  Google Scholar 

  10. Deshpande MV, Eriksson KE, Pettersson LG (1984) An assay for selective determination of exo-1,4,-beta-glucanases in a mixture of cellulolytic enzymes. Anal Biochem 138(2):481–487

    Article  PubMed  CAS  Google Scholar 

  11. Eberharter A, Sterner DE, Schieltz D, Hassan A, Yates JR 3rd, Berger SL, Workman JL (1999) The ADA complex is a distinct histone acetyltransferase complex in Saccharomyces cerevisiae. Mol Cell Biol 19(10):6621–6631

    PubMed  CAS  Google Scholar 

  12. Georgakopoulos T, Thireos G (1992) Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription. EMBO J 11(11):4145–4152

    PubMed  CAS  Google Scholar 

  13. Grant PA, Duggan L, Cote J, Roberts SM, Brownell JE, Candau R, Ohba R, Owen-Hughes T, Allis CD, Winston F, Berger SL, Workman JL (1997) Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex. Genes Dev 11(13):1640–1650

    Article  PubMed  CAS  Google Scholar 

  14. Gregory PD, Schmid A, Zavari M, Lui L, Berger SL, Horz W (1998) Absence of Gcn5 HAT activity defines a novel state in the opening of chromatin at the PHO5 promoter in yeast. Mol Cell 1(4):495–505

    Article  PubMed  CAS  Google Scholar 

  15. Grimaldi B, Coiro P, Filetici P, Berge E, Dobosy JR, Freitag M, Selker EU, Ballario P (2006) The Neurospora crassa White Collar-1 dependent blue light response requires acetylation of histone H3 lysine 14 by NGF-1. Mol Biol Cell 17(10):4576–4583

    Article  PubMed  CAS  Google Scholar 

  16. Guangtao Z, Hartl L, Schuster A, Polak S, Schmoll M, Wang T, Seidl V, Seiboth B (2009) Gene targeting in a nonhomologous end joining deficient Hypocrea jecorina. J Biotechnol 139(2):146–151

    Article  PubMed  CAS  Google Scholar 

  17. Guo J, Huang G, Cha J, Liu Y (2010) Biochemical methods used to study the gene expression and protein complexes in the filamentous fungus Neurospora crassa. Methods Mol Biol 638:189–200

    Article  PubMed  Google Scholar 

  18. Hargreaves DC, Horng T, Medzhitov R (2009) Control of inducible gene expression by signal-dependent transcriptional elongation. Cell 138(1):129–145

    Article  PubMed  CAS  Google Scholar 

  19. Hettmann C, Soldati D (1999) Cloning and analysis of a Toxoplasma gondii histone acetyltransferase: a novel chromatin remodelling factor in Apicomplexan parasites. Nucleic Acids Res 27(22):4344–4352

    Article  PubMed  CAS  Google Scholar 

  20. Howe L, Auston D, Grant P, John S, Cook RG, Workman JL, Pillus L (2001) Histone H3 specific acetyltransferases are essential for cell cycle progression. Genes Dev 15(23):3144–3154

    Article  PubMed  CAS  Google Scholar 

  21. Huisinga KL, Pugh BF (2004) A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae. Mol Cell 13(4):573–585

    Article  PubMed  CAS  Google Scholar 

  22. Jeninga EH, Schoonjans K, Auwerx J (2010) Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility. Oncogene 29(33):4617–4624

    Article  PubMed  CAS  Google Scholar 

  23. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293(5532):1074–1080

    Article  PubMed  CAS  Google Scholar 

  24. Jiang J, Lu J, Lu D, Liang Z, Li L, Ouyang S, Kong X, Jiang H, Shen B, Luo C (2012) Investigation of the acetylation mechanism by GCN5 histone acetyltransferase. PLoS ONE 7(5):e36660

    Article  PubMed  CAS  Google Scholar 

  25. Krebs JE, Peterson CL (2000) Understanding “active” chromatin: a historical perspective of chromatin remodeling. Crit Rev Eukaryot Gene Expr 10(1):1–12

    Article  PubMed  CAS  Google Scholar 

  26. Lee KK, Workman JL (2007) Histone acetyltransferase complexes: one size doesn’t fit all. Nat Rev Mol Cell Biol 8(4):284–295

    Article  PubMed  CAS  Google Scholar 

  27. Lee TI, Causton HC, Holstege FC, Shen WC, Hannett N, Jennings EG, Winston F, Green MR, Young RA (2000) Redundant roles for the TFIID and SAGA complexes in global transcription. Nature 405(6787):701–704

    Article  PubMed  CAS  Google Scholar 

  28. Lynd LR, van Zyl WH, McBride JE, Laser M (2005) Consolidated bioprocessing of cellulosic biomass: an update. Curr Opin Biotechnol 16(5):577–583

    Article  PubMed  CAS  Google Scholar 

  29. Lynd LR, Weimer PJ, van Zyl WH, Pretorius IS (2002) Microbial cellulose utilization: fundamentals and biotechnology. Microbiol Mol Biol Rev 66(3):506–577

    Article  PubMed  CAS  Google Scholar 

  30. Mandels MM, Andreotti RE (1978) Problems and challenges in the cellulose to cellulase fermentation. Process Biochem 13:6–13

    CAS  Google Scholar 

  31. Mizzen CA, Allis CD (1998) Linking histone acetylation to transcriptional regulation. Cell Mol Life Sci 54(1):6–20

    Article  PubMed  CAS  Google Scholar 

  32. Nagy Z, Tora L (2007) Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation. Oncogene 26(37):5341–5357

    Article  PubMed  CAS  Google Scholar 

  33. Nutzmann HW, Reyes-Dominguez Y, Scherlach K, Schroeckh V, Horn F, Gacek A, Schumann J, Hertweck C, Strauss J, Brakhage AA (2011) Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation. Proc Natl Acad Sci USA 108(34):14282–14287

    Article  PubMed  CAS  Google Scholar 

  34. O’Meara TR, Hay C, Price MS, Giles S, Alspaugh JA (2010) Cryptococcus neoformans histone acetyltransferase Gcn5 regulates fungal adaptation to the host. Eukaryot Cell 9(8):1193–1202

    Article  PubMed  Google Scholar 

  35. Reyes-Dominguez Y, Narendja F, Berger H, Gallmetzer A, Fernandez-Martin R, Garcia I, Scazzocchio C, Strauss J (2008) Nucleosome positioning and histone H3 acetylation are independent processes in the Aspergillus nidulans prnDprnB bidirectional promoter. Eukaryot Cell 7(4):656–663

    Article  PubMed  CAS  Google Scholar 

  36. Rose MD, Winston F, Heiter P (1990) Methods in yeast genetics: a laboratory course manual. Cold Spring Harbor Laboratory, New York

    Google Scholar 

  37. Schuster A, Tisch D, Seidl-Seiboth V, Kubicek CP, Schmoll M (2012) Roles of protein kinase A and adenylate cyclase in light-modulated cellulase regulation in Trichoderma reesei. Appl Environ Microbiol 78(7):2168–2178

    Article  PubMed  CAS  Google Scholar 

  38. Seiboth B, Karimi RA, Phatale PA, Linke R, Hartl L, Sauer DG, Smith KM, Baker SE, Freitag M, Kubicek CP (2012) The putative protein methyltransferase LAE1 controls cellulase gene expression in Trichoderma reesei. Mol Microbiol 84(6):1150–1164

    Article  PubMed  CAS  Google Scholar 

  39. Smith ER, Belote JM, Schiltz RL, Yang XJ, Moore PA, Berger SL, Nakatani Y, Allis CD (1998) Cloning of Drosophila GCN5: conserved features among metazoan GCN5 family members. Nucleic Acids Res 26(12):2948–2954

    Article  PubMed  CAS  Google Scholar 

  40. Sterner DE, Grant PA, Roberts SM, Duggan LJ, Belotserkovskaya R, Pacella LA, Winston F, Workman JL, Berger SL (1999) Functional organization of the yeast SAGA complex: distinct components involved in structural integrity, nucleosome acetylation, and TATA-binding protein interaction. Mol Cell Biol 19(1):86–98

    PubMed  CAS  Google Scholar 

  41. Struhl K (1999) Fundamentally different logic of gene regulation in eukaryotes and prokaryotes. Cell 98(1):1–4

    Article  PubMed  CAS  Google Scholar 

  42. Turner EL, Malo ME, Pisclevich MG, Dash MD, Davies GF, Arnason TG, Harkness TA (2010) The Saccharomyces cerevisiae anaphase-promoting complex interacts with multiple histone-modifying enzymes to regulate cell cycle progression. Eukaryot Cell 9(10):1418–1431

    Article  PubMed  CAS  Google Scholar 

  43. Utley RT, Ikeda K, Grant PA, Cote J, Steger DJ, Eberharter A, John S, Workman JL (1998) Transcriptional activators direct histone acetyltransferase complexes to nucleosomes. Nature 394(6692):498–502

    Article  PubMed  CAS  Google Scholar 

  44. Wade PA, Pruss D, Wolffe AP (1997) Histone acetylation: chromatin in action. Trends Biochem Sci 22(4):128–132

    Article  PubMed  CAS  Google Scholar 

  45. Wang L, Liu L, Berger SL (1998) Critical residues for histone acetylation by Gcn5, functioning in Ada and SAGA complexes, are also required for transcriptional function in vivo. Genes Dev 12(5):640–653

    Article  PubMed  CAS  Google Scholar 

  46. Wang L, Mizzen C, Ying C, Candau R, Barlev N, Brownell J, Allis CD, Berger SL (1997) Histone acetyltransferase activity is conserved between yeast and human GCN5 and is required for complementation of growth and transcriptional activation. Mol Cell Biol 17(1):519–527

    PubMed  CAS  Google Scholar 

  47. Wareski P, Vaarmann A, Choubey V, Safiulina D, Liiv J, Kuum M, Kaasik A (2009) PGC-1{alpha} and PGC-1{beta} regulate mitochondrial density in neurons. J Biol Chem 284(32):21379–21385

    Article  PubMed  CAS  Google Scholar 

  48. Waters R, Reed SH, Yu Y, Teng Y (2008) Chromatin modifications and nucleotide excision repair. SEB Exp Biol Ser 59:189–201

    PubMed  CAS  Google Scholar 

  49. Workman JL, Kingston RE (1998) Alteration of nucleosome structure as a mechanism of transcriptional regulation. Annu Rev Biochem 67:545–579

    Article  PubMed  CAS  Google Scholar 

  50. Xue-Franzen Y, Johnsson A, Brodin D, Henriksson J, Burglin TR, Wright AP (2010) Genome-wide characterisation of the Gcn5 histone acetyltransferase in budding yeast during stress adaptation reveals evolutionarily conserved and diverged roles. BMC Genomics 11:200

    Article  PubMed  Google Scholar 

  51. Zeilinger S, Schmoll M, Pail M, Mach RL, Kubicek CP (2003) Nucleosome transactions on the Hypocrea jecorina (Trichoderma reesei) cellulase promoter cbh2 associated with cellulase induction. Mol Genet Genomics 270(1):46–55

    Article  PubMed  CAS  Google Scholar 

  52. Zhang J, Zhang Y, Zhong Y, Qu Y, Wang T (2012) Ras GTPases modulate morphogenesis, sporulation and cellulase gene expression in the cellulolytic fungus Trichoderma reesei. PLoS ONE 7(11):e48786

    Article  PubMed  CAS  Google Scholar 

  53. Zhou Q, Xu J, Kou Y, Lv X, Zhang X, Zhao G, Zhang W, Chen G, Liu W (2012) Differential involvement of beta-glucosidases from Hypocrea jecorina in rapid induction of cellulase genes by cellulose and cellobiose. Eukaryot Cell 11(11):1371–1381

    Article  PubMed  CAS  Google Scholar 

  54. Zupkovitz G, Tischler J, Posch M, Sadzak I, Ramsauer K, Egger G, Grausenburger R, Schweifer N, Chiocca S, Decker T, Seiser C (2006) Negative and positive regulation of gene expression by mouse histone deacetylase 1. Mol Cell Biol 26(21):7913–7928

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Prof. J. Andrew Alspaugh for providing the yeast gcn5Δ strain. This study is supported by grants from the National Basic Research Program of China (2011CB707402), the National Natural Science Foundation (31270116), the Shandong Provincial Funds for Distinguished Young Scientists (JQ201108), New Century Excellent Talents in University (NCET-10-0546), and Independent Innovation Foundation of Shandong University, IIFSDU.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Weifeng Liu.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 50 kb)

Supplementary material 2 (DOC 35 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xin, Q., Gong, Y., Lv, X. et al. Trichoderma reesei Histone Acetyltransferase Gcn5 Regulates Fungal Growth, Conidiation, and Cellulase Gene Expression. Curr Microbiol 67, 580–589 (2013). https://doi.org/10.1007/s00284-013-0396-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-013-0396-4

Keywords

Navigation