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Title: Functional Analyses of Trichoderma reesei LAE1 Reveal Conserved and Contrasting Roles of This Regulator

Abstract

The putative methyltransferase LaeA is a global regulator that affects the expression of multiple secondary metabolite gene clusters in several fungi, and it can modify heterochromatin structure in Aspergillus nidulans. We have recently shown that the LaeA ortholog of Trichoderma reesei (LAE1), a fungus that is an industrial producer of cellulase and hemicellulase enzymes, regulates the expression of cellulases and polysaccharide hydrolases. To learn more about the function of LAE1 in T. reesei, we analyzied the effect of deletion and overexpression of lae1 on genome-wide gene expression. We discovered that in addition to positively regulating 7 of 17 polyketide or nonribosomal peptide synthases, genes encoding ankyrin-proteins, iron uptake, heterokaryon incompatibility proteins, PTH11-receptors, and oxidases/monoxygenases are major gene categories also regulated by LAE1. chromatin immunoprecipitation sequencing with antibodies against histone modifications known to be associated with transcriptionally active (H3K4me2 and -me3) or silent (H3K9me3) chromatin detected 4089 genes bearing one or more of these methylation marks, of which 75 exhibited a correlation between either H3K4me2 or H3K4me3 and regulation by LAE1. Transformation of a laeA-null mutant of A. nidulans with the T. reesei lae1 gene did not rescue sterigmatocystin formation and further impaired sexual development. LAE1 did not interact with A.more » nidulans VeA in yeast two-hybrid assays, whereas it interacted with the T. reesei VeA ortholog, VEL1. LAE1 was shown to be required for the expression of vel1, whereas the orthologs of velB and VosA are unaffected by lae1 deletion. Our data show that the biological roles of A. nidulans LaeA and T. reesei LAE1 are much less conserved than hitherto thought. In T. reesei, LAE1 appears predominantly to regulate genes increasing relative fitness in its environment.« less

Authors:
 [1];  [2];  [3];  [3]; ORCiD logo [4];  [1];  [1];  [1];  [1];  [2];  [2];  [4];  [1]
  1. Vienna Univ. of Technology (Austria)
  2. Univ. of Wisconsin-Madison, Madison, WI (United States)
  3. Oregon State Univ., Corvallis, OR (United States)
  4. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1557228
Report Number(s):
PNNL-SA-94192
Journal ID: ISSN 2160-1836
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
G3
Additional Journal Information:
Journal Volume: 3; Journal Issue: 2; Journal ID: ISSN 2160-1836
Publisher:
Genetics Society of America
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Trichoderma; epigenetic

Citation Formats

Karimi-Aghcheh, Razieh, Bok, Jin Woo, Phatale, Pallavi A., Smith, Kristina M., Baker, Scott E., Lichius, Alexander, Omann, Markus, Zeilinger, Susanne, Seiboth, Bernhard, Rhee, Catherine, Keller, Nancy P., Freitag, Michael, and Kubicek, Christian P. Functional Analyses of Trichoderma reesei LAE1 Reveal Conserved and Contrasting Roles of This Regulator. United States: N. p., 2013. Web. doi:10.1534/g3.112.005140.
Karimi-Aghcheh, Razieh, Bok, Jin Woo, Phatale, Pallavi A., Smith, Kristina M., Baker, Scott E., Lichius, Alexander, Omann, Markus, Zeilinger, Susanne, Seiboth, Bernhard, Rhee, Catherine, Keller, Nancy P., Freitag, Michael, & Kubicek, Christian P. Functional Analyses of Trichoderma reesei LAE1 Reveal Conserved and Contrasting Roles of This Regulator. United States. doi:10.1534/g3.112.005140.
Karimi-Aghcheh, Razieh, Bok, Jin Woo, Phatale, Pallavi A., Smith, Kristina M., Baker, Scott E., Lichius, Alexander, Omann, Markus, Zeilinger, Susanne, Seiboth, Bernhard, Rhee, Catherine, Keller, Nancy P., Freitag, Michael, and Kubicek, Christian P. Fri . "Functional Analyses of Trichoderma reesei LAE1 Reveal Conserved and Contrasting Roles of This Regulator". United States. doi:10.1534/g3.112.005140. https://www.osti.gov/servlets/purl/1557228.
@article{osti_1557228,
title = {Functional Analyses of Trichoderma reesei LAE1 Reveal Conserved and Contrasting Roles of This Regulator},
author = {Karimi-Aghcheh, Razieh and Bok, Jin Woo and Phatale, Pallavi A. and Smith, Kristina M. and Baker, Scott E. and Lichius, Alexander and Omann, Markus and Zeilinger, Susanne and Seiboth, Bernhard and Rhee, Catherine and Keller, Nancy P. and Freitag, Michael and Kubicek, Christian P.},
abstractNote = {The putative methyltransferase LaeA is a global regulator that affects the expression of multiple secondary metabolite gene clusters in several fungi, and it can modify heterochromatin structure in Aspergillus nidulans. We have recently shown that the LaeA ortholog of Trichoderma reesei (LAE1), a fungus that is an industrial producer of cellulase and hemicellulase enzymes, regulates the expression of cellulases and polysaccharide hydrolases. To learn more about the function of LAE1 in T. reesei, we analyzied the effect of deletion and overexpression of lae1 on genome-wide gene expression. We discovered that in addition to positively regulating 7 of 17 polyketide or nonribosomal peptide synthases, genes encoding ankyrin-proteins, iron uptake, heterokaryon incompatibility proteins, PTH11-receptors, and oxidases/monoxygenases are major gene categories also regulated by LAE1. chromatin immunoprecipitation sequencing with antibodies against histone modifications known to be associated with transcriptionally active (H3K4me2 and -me3) or silent (H3K9me3) chromatin detected 4089 genes bearing one or more of these methylation marks, of which 75 exhibited a correlation between either H3K4me2 or H3K4me3 and regulation by LAE1. Transformation of a laeA-null mutant of A. nidulans with the T. reesei lae1 gene did not rescue sterigmatocystin formation and further impaired sexual development. LAE1 did not interact with A. nidulans VeA in yeast two-hybrid assays, whereas it interacted with the T. reesei VeA ortholog, VEL1. LAE1 was shown to be required for the expression of vel1, whereas the orthologs of velB and VosA are unaffected by lae1 deletion. Our data show that the biological roles of A. nidulans LaeA and T. reesei LAE1 are much less conserved than hitherto thought. In T. reesei, LAE1 appears predominantly to regulate genes increasing relative fitness in its environment.},
doi = {10.1534/g3.112.005140},
journal = {G3},
number = 2,
volume = 3,
place = {United States},
year = {2013},
month = {2}
}

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Works referenced in this record:

An investigation of the nuclei of hülle cells of Aspergillus nidulans
journal, January 2002


Trichoderma: the genomics of opportunistic success
journal, September 2011

  • Druzhinina, Irina S.; Seidl-Seiboth, Verena; Herrera-Estrella, Alfredo
  • Nature Reviews Microbiology, Vol. 9, Issue 10
  • DOI: 10.1038/nrmicro2637

Effects of laeA deletion on Aspergillus flavus conidial development and hydrophobicity may contribute to loss of aflatoxin production
journal, February 2012


Requirement of LaeA for secondary metabolism and sclerotial production in Aspergillus flavus
journal, October 2008

  • Kale, Shubha P.; Milde, Lane; Trapp, Marisa K.
  • Fungal Genetics and Biology, Vol. 45, Issue 10, p. 1422-1429
  • DOI: 10.1016/j.fgb.2008.06.009

Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA increases activation of secondary metabolite production
journal, August 2012


Neurospora crassa ve-1 affects asexual conidiation
journal, February 2008

  • Bayram, Özgür; Krappmann, Sven; Seiler, Stephan
  • Fungal Genetics and Biology, Vol. 45, Issue 2
  • DOI: 10.1016/j.fgb.2007.06.001

Genomic Mining for Aspergillus Natural Products
journal, January 2006


Genome-wide high throughput analysis of DNA methylation in eukaryotes
journal, March 2009


VelB/VeA/LaeA Complex Coordinates Light Signal with Fungal Development and Secondary Metabolism
journal, June 2008


LaeA, a Regulator of Morphogenetic Fungal Virulence Factors
journal, September 2005


Role of laeA in the Regulation of alb1 , gliP , Conidial Morphology, and Virulence in Aspergillus fumigatus
journal, July 2007

  • Sugui, Janyce A.; Pardo, Julian; Chang, Yun C.
  • Eukaryotic Cell, Vol. 6, Issue 9
  • DOI: 10.1128/EC.00140-07

Coordination of secondarymetabolism and development in fungi: the velvet familyof regulatory proteins
journal, January 2012


Lae1 regulates expression of multiple secondary metabolite gene clusters in Fusarium verticillioides
journal, August 2012

  • Butchko, Robert A. E.; Brown, Daren W.; Busman, Mark
  • Fungal Genetics and Biology, Vol. 49, Issue 8, p. 602-612
  • DOI: 10.1016/j.fgb.2012.06.003

Distinct Roles for VeA and LaeA in Development and Pathogenesis of Aspergillus flavus
journal, May 2009


Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa
journal, December 2008

  • Lewis, Z. A.; Honda, S.; Khlafallah, T. K.
  • Genome Research, Vol. 19, Issue 3
  • DOI: 10.1101/gr.086231.108

FgVELB is associated with vegetative differentiation, secondary metabolism and virulence in Fusarium graminearum
journal, August 2012


Phylogenomic analysis of polyketide synthase-encoding genes in Trichoderma
journal, November 2011


Regulation of secondary metabolism by chromatin structure and epigenetic codes
journal, January 2011


A comparison of normalization methods for high density oligonucleotide array data based on variance and bias
journal, January 2003


LaeA Control of Velvet Family Regulatory Proteins for Light-Dependent Development and Fungal Cell-Type Specificity
journal, December 2010

  • Sarikaya Bayram, Özlem; Bayram, Özgür; Valerius, Oliver
  • PLoS Genetics, Vol. 6, Issue 12, Article No. e1001226
  • DOI: 10.1371/journal.pgen.1001226

Summaries of Affymetrix GeneChip probe level data
journal, February 2003


Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans
journal, February 2010


Structure of the Conserved Core of the Yeast Dot1p, a Nucleosomal Histone H3 Lysine 79 Methyltransferase
journal, July 2004

  • Sawada, Ken; Yang, Zhe; Horton, John R.
  • Journal of Biological Chemistry, Vol. 279, Issue 41
  • DOI: 10.1074/jbc.M405902200

The putative protein methyltransferase LAE1 controls cellulase gene expression in Trichoderma reesei: Cellulase regulation in T. reesei
journal, May 2012


Aspergillus oryzae laeA Regulates Kojic Acid Synthesis Genes
journal, September 2011

  • Oda, Ken; Kobayashi, Akiko; Ohashi, Shinichi
  • Bioscience, Biotechnology, and Biochemistry, Vol. 75, Issue 9, p. 1832-1834
  • DOI: 10.1271/bbb.110235

A histone H3 methyltransferase controls DNA methylation in Neurospora crassa
journal, November 2001

  • Tamaru, Hisashi; Selker, Eric U.
  • Nature, Vol. 414, Issue 6861
  • DOI: 10.1038/35104508

The FunCat, a functional annotation scheme for systematic classification of proteins from whole genomes
journal, October 2004


Secondary Metabolism and Development Is Mediated by LlmF Control of VeA Subcellular Localization in Aspergillus nidulans
journal, January 2013


LaeA, a Regulator of Secondary Metabolism in Aspergillus spp.
journal, April 2004


RF cloning: A restriction-free method for inserting target genes into plasmids
journal, April 2006

  • van den Ent, Fusinita; Löwe, Jan
  • Journal of Biochemical and Biophysical Methods, Vol. 67, Issue 1
  • DOI: 10.1016/j.jbbm.2005.12.008

Transcriptional Regulation of Chemical Diversity in Aspergillus fumigatus by LaeA
journal, January 2007


Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease
journal, November 1979

  • Chirgwin, John M.; Przybyla, Alan E.; MacDonald, Raymond J.
  • Biochemistry, Vol. 18, Issue 24
  • DOI: 10.1021/bi00591a005

Roles of Protein Kinase A and Adenylate Cyclase in Light-Modulated Cellulase Regulation in Trichoderma reesei
journal, January 2012

  • Schuster, André; Tisch, Doris; Seidl-Seiboth, Verena
  • Applied and Environmental Microbiology, Vol. 78, Issue 7
  • DOI: 10.1128/AEM.06959-11

Accurate prediction of the Aspergillus nidulans terrequinone gene cluster boundaries using the transcriptional regulator LaeA
journal, November 2007

  • Bouhired, Sarah; Weber, Monika; Kempf-Sontag, Anita
  • Fungal Genetics and Biology, Vol. 44, Issue 11, p. 1134-1145
  • DOI: 10.1016/j.fgb.2006.12.010

Beyond aflatoxin: four distinct expression patterns and functional roles associated with Aspergillus flavus secondary metabolism gene clusters
journal, March 2010


A Circadian Oscillator in Aspergillus spp . Regulates Daily Development and Gene Expression
journal, April 2003


The global regulator LaeA controls penicillin biosynthesis, pigmentation and sporulation, but not roquefortine C synthesis in Penicillium chrysogenum
journal, February 2009


Heterochromatin Is Required for Normal Distribution of Neurospora crassa CenH3
journal, April 2011

  • Smith, K. M.; Phatale, P. A.; Sullivan, C. M.
  • Molecular and Cellular Biology, Vol. 31, Issue 12
  • DOI: 10.1128/MCB.01285-10

Wolbachia: intracellular manipulators of mite reproduction
journal, August 1996

  • Breeuwer, J. A. J.; Jacobs, G.
  • Experimental and Applied Acarology, Vol. 20, Issue 8
  • DOI: 10.1007/BF00053306

The G-Alpha Protein GNA3 of Hypocrea jecorina (Anamorph Trichoderma reesei ) Regulates Cellulase Gene Expression in the Presence of Light
journal, January 2009

  • Schmoll, Monika; Schuster, André; Silva, Roberto do Nascimento
  • Eukaryotic Cell, Vol. 8, Issue 3
  • DOI: 10.1128/EC.00256-08

Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina)
journal, May 2008

  • Martinez, Diego; Berka, Randy M.; Henrissat, Bernard
  • Nature Biotechnology, Vol. 26, Issue 5
  • DOI: 10.1038/nbt1403

Histone arginine methylation
journal, November 2010


Novel traits of Trichoderma predicted through the analysis of its secretome
journal, September 2012


Secondary metabolic gene cluster silencing in Aspergillus nidulans
journal, September 2006


Methylation of Histone H3 Lysine 36 Is Required for Normal Development in Neurospora crassa
journal, August 2005


Trimethylated lysine 9 of histone H3 is a mark for DNA methylation in Neurospora crassa
journal, April 2003

  • Tamaru, Hisashi; Zhang, Xing; McMillen, Debra
  • Nature Genetics, Vol. 34, Issue 1
  • DOI: 10.1038/ng1143

    Works referencing / citing this record:

    Several steps of lateral gene transfer followed by events of ‘birth-and-death’ evolution shaped a fungal sorbicillinoid biosynthetic gene cluster
    journal, December 2016

    • Druzhinina, Irina S.; Kubicek, Eva M.; Kubicek, Christian P.
    • BMC Evolutionary Biology, Vol. 16, Issue 1
    • DOI: 10.1186/s12862-016-0834-6