Abstract
Filamentous fungi are today a major source of industrial biotechnology for the production of primary and secondary metabolites, as well as enzymes and recombinant proteins. All of them have undergone extensive improvement strain programs, initially by classical mutagenesis and later on by genetic manipulation. Thereby, strategies to overcome rate-limiting or yield-reducing reactions included manipulating the expression of individual genes, their regulatory genes, and also their function. Yet, research of the last decade clearly showed that cells can also undergo heritable changes in gene expression that do not involve changes in the underlying DNA sequences (=epigenetics). This involves three levels of regulation: (i) DNA methylation, (ii) chromatin remodeling by histone modification, and (iii) RNA interference. The demonstration of the occurrence of these processes in fungal model organisms such as Aspergillus nidulans and Neurospora crassa has stimulated its recent investigation as a tool for strain improvement in industrially used fungi. This review describes the progress that has thereby been obtained.
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References
Adhvaryu KK, Morris SA, Strahl BD, Selker EU (2005) Methylation of histone H3 lysine 36 is required for normal development in Neurospora crassa. Eukaryot Cell 4(8):1455–1464
Aimiuwu J, Wang H, Chen P, Xie Z, Wang J, Liu S, Klisovic R, Mims A, Blum W, Marcucci G, Chan KK (2012) RNA-dependent inhibition of ribonucleotide reductase is a major pathway for 5-azacytidine activity in acute myeloid leukemia. Blood 119(22):5229–5238. doi:10.1182/blood-2011-11-382226
Alexander WG, Raju NB, Xiao H, Hammond TM, Perdue TD, Metzenberg RL, Pukkila PJ, Shiu PK (2008) DCL-1 colocalizes with other components of the MSUD machinery and is required for efficient silencing in Neurospora crassa. Fungal Genet Biol 45:719–727
Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, Dreyfuss G, Eddy SR, Griffiths-Jones S, Marshall M, Matzke M, Ruvkun G, Tuschl T (2003) A uniform system for microRNA annotation. RNA 9:277–279
Antequera F, Tamame M, Villanueva JR, Santos T (1984) DNA methylation in the fungi. J Biol Chem 259:8033–8036
Aronson BD, Johnson KA, Dunlap JC (1994) Circadian clock locus frequency: protein encoded by a single open reading frame defines period length and temperature compensation. Proc Natl Acad Sci U S A 91(16):7683–7687
Arthanari Y, Heintzen C, Griffiths-Jones S, Crosthwaite SK (2014) Natural antisense transcripts and long non-coding RNA in Neurospora crassa. PLoS One 9(3), e91353. doi:10.1371/journal.pone.0091353
Baba S, Kinoshita H, Nihira T (2012) Identification and characterization of Penicillium citrinum VeA and LaeA as global regulators for ML-236B production. Curr Genet 58(1):1–11. doi:10.1007/s00294-011-0359-x
Baker CL, Loros JJ, Dunlap JC (2011) The circadian clock of Neurospora crassa. FEMS Microbiol Rev. doi:10.1111/j.1574-6976.2011.00288.x
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Bayram Ö, Braus GH (2011) Coordination of secondary metabolism and development in fungi: the velvet family of regulatory proteins. FEMS Microbiol Rev 36(1):1–24. doi:10.1111/j.1574-6976.2011.00285
Bayram Ö, Krappmann S, Ni M, Bok JW, Helmstaedt K, Valerius O, Braus-Stromeyer S, Kwon NJ, Keller NP, Yu JH, Braus GH (2008) VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science 320(5882):1504–1506. doi:10.1126/science.1155888
Beisler JA (1978) Isolation, characterization, and properties of a labile hydrolysis product of the antitumor nucleoside, 5-azacytidine. J Med Chem 21:204–208
Belden WJ, Loros JJ, Dunlap JC (2007) Execution of the circadian negative feedback loop in Neurospora requires the ATP-dependent chromatin remodeling enzyme CLOCKSWITCH. Mol Cell 25:587–600
Belden WJ, Lewis ZA, Selker EU, Loros JJ, Dunlap JC (2011) CHD1 remodels chromatin and influences transient DNA methylation at the clock gene frequency. PLoS Genet 7(7), e1002166. doi:10.1371/journal.pgen.1002166
Bernstein DA, Vyas VK, Weinberg DE, Drinnenberg IA, Bartel DP, Fink GR (2012) Candida albicans Dicer (CaDcr1) is required for efficient ribosomal and spliceosomal RNA maturation. Proc Natl Acad Sci U S A 109(2):523–528. doi:10.1073/pnas.1118859109
Böhm J, Hoff B, O’Gorman CM, Wolfers S, Klix V, Binger D, Zadra I, Kürnsteiner H, Pöggeler S, Dyer PS, Kück U (2013) Sexual reproduction and mating-type–mediated strain development in the penicillin-producing fungus Penicillium chrysogenum. Proc Natl Acad Sci U S A 110(4):1476–1481. doi:10.1073/pnas.1217943110
Bok JW, Keller NP (2004) LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot Cell 3(2):527–535
Bok JW, Chiang YM, Szewczyk E, Reyes-Dominguez Y, Davidson AD, Sanchez JF, Lo HC, Watanabe K, Strauss J, Oakley BR, Wang CC, Keller NP (2009) Chromatin-level regulation of biosynthetic gene clusters. Nat Chem Biol 5(7):462–464. doi:10.1038/nchembio.177
Bonasio R (2015) The expanding epigenetic landscape of non-model organisms. J Exp Biol 218(Pt 1):114–122. doi:10.1242/jeb.110809
Brakhage AA, Thön M, Spröte P, Scharf DH, Al-Abdallah Q, Wolke SM, Hortschansky P (2009) Aspects on evolution of fungal beta-lactam biosynthesis gene clusters and recruitment of trans-acting factors. Phytochemistry 70(15-16):1801–1811. doi:10.1016/j.phytochem.2009.09.011
Braumann I, van den Berg M, Kempken F (2008) Repeat induced point mutation in two asexual fungi, Aspergillus niger and Penicillium chrysogenum. Curr Genet 53(5):287–297. doi:10.1007/s00294-008-0185-y
Brosch G, Loidl P, Graessle S (2008) Histone modifications and chromatin dynamics: a focus on filamentous fungi. FEMS Microbiol Rev 32:409–439
Cambareri EB, Jensen BC, Schabtach E, Selker EU (1989) Repeat-induced G-C to A-T mutations in Neurospora. Science 244:1571–1575
Campos E, Reinberg D (2009) Histones: annotating chromatin. Annu Rev Genet 43:559–599. doi:10.1146/annurev.genet.032608.103928
Chakravarti R, Sahai V (2004) Compactin—a review. Appl Microbiol Biotechnol 64(5):618–624
Chen PY, Montanini B, Liao WW, Morselli M, Jaroszewicz A, Lopez D, Ottonello S, Pellegrini MA (2014) Comprehensive resource of genomic, epigenomic and transcriptomic sequencing data for the black truffle Tuber melanosporum. Gigascience 3:25. doi:10.1186/2047-217X-3-25
Chernov AV, Vollmayr P, Walter J, Trautner TA (1997) Masc2, a C5-DNA-methyltransferase from Ascobolus immersus with similarity to methyltransferases of higher organisms. Biol Chem 378(12):1467–1473
Chung YM, Wei CK, Chuang DW, El-Shazly M, Hsieh CT, Asai T, Oshima Y, Hsieh TJ, Hwang TL, Wu YC, Chang FR (2013) An epigenetic modifier enhances the production of anti-diabetic and anti-inflammatory sesquiterpenoids from Aspergillus sydowii. Bioorg Med Chem 21(13):3866–3872. doi:10.1016/j.bmc.2013.04.004
Clarke AS, Lowell JE, Jacobson SJ, Pillus L (1999) Esa1p is an essential histone acetyltransferase required for cell cycle progression. Mol Cell Biol 19(4):2515–2526
Clutterbuck JA, Kapitonov VV, Jurka J (2008) Transposable elements and repeat induced point mutation in Aspergillus nidulans, Aspergillus fumigatus, and Aspergillus oryzae. In: Osmani SA, Goldman GH (eds) The Aspergilli: genomics, medical aspects, biotechnology, and research methods. CRC Press, Boca Raton, pp 343–355
Connolly LR, Smith KM, Freitag M (2013) The Fusarium graminearum histone H3 K27 methyltransferase KMT6 regulates development and expression of secondary metabolite gene clusters. PLoS Genet 9(10), e1003916. doi:10.1371/journal.pgen.1003916
Dang Y, Yang Q, Xue Z, Liu Y (2011) RNA interference in fungi: pathways, functions, and applications. Eukaryot Cell 10(9):1148–1155. doi:10.1128/EC.05109-11
Dashtban M, Schraft H, Qin W (2009) Fungal bioconversion of lignocellulosic residues; opportunities & perspectives. Int J Biol Sci 5(6):578–595
de Haro JP, Calo S, Cervantes M, Nicolás FE, Torres-Martínez S, Ruiz-Vázquez RM (2009) A single dicer gene is required for efficient gene silencing associated with two classes of small antisense RNAs in Mucor circinelloides. Eukaryot Cell 8(10):1486–1497. doi:10.1128/EC.00191-09
Delmas S, Pullan ST, Gaddipati S, Kokolski M, Malla S, Blythe MJ, Ibbett R, Campbell M, Liddell S, Aboobaker A, Tucker GA, Archer DB (2012) Uncovering the genome-wide transcriptional responses of the filamentous fungus Aspergillus niger to lignocellulose using RNA sequencing. PLoS Genet 8(8), e1002875. doi:10.1371/journal.pgen.1002875
Donaldson ME, Saville BJ (2012) Natural antisense transcripts in fungi. Mol Microbiol 85(3):405–417. doi:10.1111/j.1365-2958.2012.08125.x
Dreyer J, Eichhorn H, Friedlin E, Kürnsteiner H, Kück U (2007) A homologue of the Aspergillus velvet gene regulates both cephalosporin C biosynthesis and hyphal fragmentation in Acremonium chrysogenum. Appl Environ Microbiol 73(10):3412–3422
Drinnenberg IA, Weinberg DE, Xie KT, Mower JP, Wolfe KH, Fink GR, Bartel DP (2009) RNAi in budding yeast. Science 326:544–550. doi:10.1126/science.1176945
Duran RM, Gregersen S, Smith TD, Bhetariya PJ, Cary JW, Harris-Coward PY, Mattison CP, Grimm C, Calvo AM (2014) The role of Aspergillus flavus veA in the production of extracellular proteins during growth on starch substrates. Appl Microbiol Biotechnol 98(11):5081–5094. doi:10.1007/s00253-014-5598-6
Engström PG, Suzuki H, Ninomiya N, AkalinA SL, Lavorgna G, Brozzi A, Luzi L, Tan SL, Yang L, Kunarso G, Lian-Chong Ng E, Batalov S, Wahlestedt C, Kai C, Kawai J, Carninci P, Hayashizaki Y, Wells C, Bajic VB, Orlando V, Reid JF, Lenhard B, Lipovich L (2006) Complex loci in human and mouse genomes. PLoS Genet 2, e47. doi:10.1371/journal.pgen.0020047
Fekete E, Karaffa L, Karimi Aghcheh R, Neméth Z, Paholcsek M, Stagel A, Kubicek CP (2014) The transcriptome of lae1 mutants of Trichoderma reesei cultivated at constant growth rates reveals new targets of LAE1 function. BMC Genomics 15:447. doi:10.1186/1471-2164-15-447
Freitag M, Williams RL, Kothe GO, Selker EU (2002) A cytosine methyltransferase homologue is essential for repeat-induced point mutation in Neurospora crassa. Proc Natl Acad Sci U S A 99(13):8802–8807
Freitag M, Hickey PC, Khlafallah TK, Read ND, Selker EU (2004) HP1 is essential for DNA methylation in Neurospora. Mol Cells 13(3):427–434
García I, Mathieu M, Nikolaev I, Felenbok B, Scazzocchio C (2008) Roles of the Aspergillus nidulans homologues of Tup1 and Ssn6 in chromatin structure and cell viability. FEMS Microbiol Lett 289(2):146–154. doi:10.1111/j.1574-6968.2008.01379.x
Geisler S, Lojek L, Khalil AM, Baker KE, Coller J (2012) Decapping of long non-coding RNAs regulates inducible genes. Mol Cell 45(3):279–291. doi:10.1016/j.molcel.2011.11.025
Ghildiyal M, Zamore PD (2009) Small silencing RNAs: an expanding universe. Nat Rev Genet 10(2):94–108. doi:10.1038/nrg2504
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(1):14. doi:10.1186/1754-6834-7-14
Hall IM, Noma K, Grewal SI (2003) RNA interference machinery regulates chromosome dynamics during mitosis and meiosis in fission yeast. Proc Natl Acad Sci U S A 100(1):193–198
Harting R, Bayram Ö, Laubinger K, Valerius O, Braus GH (2013) Interplay of the fungal sumoylation network for control of multicellular development. Mol Microbiol 90(5):1125–1145. doi:10.1111/mmi.12421
Hasunuma K (2009) History and scope of genetics: epigenetic regulation of gene expression. In: Hasunuma K (ed) Genetics and molecular biology. Encyclopedia of life support systems publishers, developed under the auspices of the UNESCO. Eolss Publishers, Paris
Herrera CM, Pozo MI, Bazaga P (2012) Jack of all nectars, master of most: DNA methylation and the epigenetic basis of niche width in a flower-living yeast. Mol Ecol 21(11):2602–2616. doi:10.1111/j.1365-294X.2011.05402.x
Ho DH, Burggren WW (2010) Epigenetics and transgenerational transfer: a physiological perspective. J Exp Biol 213(1):3–16. doi:10.1242/jeb.019752
Hodgkin J (1994) Epigenetics and the maintenance of gene activity states in Caenorhabditis elegans. Dev Genet 15:471–477
Hoff B, Kamerewerd J, Sigl C, Mitterbauer R, Zadra I, Kürnsteiner H, Kück U (2010) Two components of a velvet-like complex control hyphal morphogenesis, conidiophore development, and penicillin biosynthesis in Penicillium chrysogenum. Eukaryot Cell 9(8):1236–1250. doi:10.1128/EC.00077-10
Honda S, Selker EU (2008) Direct interaction between DNA methyltransferase DIM-2 and HP1 is required for DNA methylation in Neurospora crassa. Mol Cell Biol 28(19):6044–6055. doi:10.1128/MCB.00823-08
Honda S, Lewis ZA, Shimada K, Fischle W, Sack R, Selker EU (2012) Heterochromatin protein 1 forms distinct complexes to direct histone deacetylation and DNA methylation. Nat Struct Mol Biol 19(5):471–477. doi:10.1038/nsmb.2274
Houseley J, Rubbi L, Grunstein M, Tollervey D, Vogelauer M (2008) A ncRNA modulates histone modification and mRNA induction in the yeast GAL gene cluster. Mol Cell 32(5):685–695. doi:10.1016/j.molcel.2008.09.027
Ikeda K, Van Vu B, Kadotani N, Tanaka M, Murata T, Shiina K, Chuma I, Tosa Y, Nakayashiki H (2013) Is the fungus Magnaporthe losing DNA methylation? Genetics 195(3):845–855. doi:10.1534/genetics.113.155978
Janbon G, Maeng S, Yang DH, Ko YJ, Jung KW, Moyrand F (2010) Characterizing the role of the RNA silencing components in Cryptococcus neoformans. Fungal Genet Biol 47(12):1070–1080. doi:10.1016/j.fgb.2010.10.005
Janus D, Hoff B, Kück U (2009) Evidence for Dicer-dependent RNA interference in the industrial penicillin producer Penicillium chrysogenum. Microbiology 155(Pt 12):3946–3956. doi:10.1099/mic.0.032763-0
Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128(4):683–692
Kadotani N, Nakayashiki H, Tosa Y, Mayama S (2004) One of the two Dicer-like proteins in the filamentous fungi Magnaporthe oryzae genome is responsible for hairpin RNA-triggered RNA silencing and related small interfering RNA accumulation. J Biol Chem 279:44467–44474
Kanduri C (2011) Long noncoding RNA and epigenomics. Adv Exp Med Biol 722:174–195. doi:10.1007/978-1-4614-0332-6_11
Karimi Aghcheh R, Bok JW, Phatale PA, Smith KM, Baker SE, Lichius A, Omann M, Zeilinger S, Seiboth B, Rhee C, Keller NP, Freitag M, Kubicek CP (2013) Functional analyses of Trichoderma reesei LAE1 reveal conserved and contrasting roles of this regulator. G3 (Bethesda) 3(2):369–378. doi:10.1534/g3.112.005140
Karimi Aghcheh R, Németh Z, Atanasova L, Fekete E, Paholcsek M, Sándor E, Aquino B, Druzhinina IS, Karaffa L, Kubicek CP (2014) The VELVET A orthologue VEL1 of Trichoderma reesei regulates fungal development and is essential for cellulase gene expression. PLoS One 9(11), e112799. doi:10.1371/journal.pone.0112799
Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, Suzuki H, Carninci P, Hayashizaki Y, Wells C, Frith M, Ravasi T, Pang KC, Hallinan J, Mattick J, Hume DA, Lipovich L, Batalov S, Engström PG, Mizuno Y, Faghihi MA, Sandelin A, Chalk AM, Mottagui-Tabar S, Liang Z, Lenhard B, Wahlestedt C (2005) Antisense transcription in the mammalian transcriptome. Science 309:1564–1566
Kopke K, Hoff B, Bloemendal S, Katschorowski A, Kamerewerd J, Kück U (2013) Members of the Penicillium chrysogenum velvet complex play functionally opposing roles in the regulation of penicillin biosynthesis and conidiation. Eukaryot Cell 12(2):299–310. doi:10.1128/EC.00272-12
Kosalková K, García-Estrada C, Ullán RV, Godio RP, Feltrer R, Teijeira F, Mauriz E, Martín JF (2009) The global regulator LaeA controls penicillin biosynthesis, pigmentation and sporulation, but not roquefortine C synthesis in Penicillium chrysogenum. Biochimie 91(2):214–225. doi:10.1016/j.biochi.2008.09.004
Kouzminova EA, Selker EU (2001) Dim-2 encodes a DNA methyltransferase responsible for all known cytosine methylation in Neurospora. EMBO J 20:4309–4323
Kramer C, Loros JJ, Dunlap JC, Crosthwaite SK (2003) Role for antisense RNA in regulating circadian clock function in Neurospora crassa. Nature 421:948
Krogan NJ, Dover J, Wood A, Schneider J, Heidt J, Boateng MA, Dean K, Ryan OW, Golshani A, Johnston M, Greenblatt JF, Shilatifard A (2003) The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. Mol Cell 11(3):721–729
Kuba-Miyara M, Yasuda M (2012) Bioorganic compounds produced by the fungus Monascus and their use in health sciences and medicine. Mini Rev Org Chem 9:11–19. doi:10.2174/157019312799080071
Kubicek CP, Herrera-Estrella A, Seidl-Seiboth V, Martinez DA, Druzhinina IS, Thon M, Zeilinger S, Casas-Flores S, Horwitz BA, Mukherjee PK, Mukherjee M, Kredics L, Alcaraz LD, Aerts A, Antal Z, Atanasova L, Cervantes-Badillo MG, Challacombe J, Chertkov O, McCluskey K, Coulpier F, Deshpande N, von Döhren H, Ebbole DJ, Esquivel-Naranjo EU, Fekete E, Flipphi M, Glaser F, Gómez-Rodríguez EY, Gruber S, Han C, Henrissat B, Hermosa R, Hernández-Oñate M, Karaffa L, Kosti I, Le Crom S, Lindquist E, Lucas S, Lübeck M, Lübeck PS, Margeot A, Metz B, Misra M, Nevalainen H, Omann M, Packer N, Perrone G, Uresti-Rivera EE, Salamov A, Schmoll M, Seiboth B, Shapiro H, Sukno S, Tamayo-Ramos JA, Tisch D, Wiest A, Wilkinson HH, Zhang M, Coutinho PM, Kenerley CM, Monte E, Baker SE, Grigoriev IV (2011) Comparative genome sequence analysis underscores mycoparasitism as the ancestral life style of Trichoderma. Genome Biol 12(4):R40. doi:10.1186/gb-2011-12-4-r40
Lee DW, Freitag M, Selker EU, Aramayo R (2008) A cytosine methyltransferase homologue is essential for sexual development in Aspergillus. nidulans. PLoS One 3(6), e2531. doi:10.1371/journal.pone.0002531
Lee HC, Li L, Gu W, Xue Z, Crosthwaite SK, Pertsemlidis A, Lewis ZA, Freitag M, Selker EU, Mello CC, Liu Y (2010) Diverse pathways generate microRNA-like RNAs and Dicer independent small interfering RNAs in fungi. Mol Cell 38(6):803–814. doi:10.1016/j.molcel.2010.04.005
Lee SS, Lee JH, Lee I (2013) Strain improvement by overexpression of the laeA gene in Monascus pilosus for the production of monascus-fermented rice. J Microbiol Biotechnol 23(7):959–965
Liu SY, Lin JQ, Wu HL, Wang CC, Huang SJ, Luo YF, Sun JH, Zhou JX, Yan SJ, He JG, Wang J, He ZM (2012) Bisulfite sequencing reveals that Aspergillus flavus holds a hollow in DNA methylation. PLoS One 7(1), e30349. doi:10.1371/journal.pone.0030349
Liu DZ, Liang BW, Li XF, Liu Q (2014) Induced production of new diterpenoids in the fungus Penicillium funiculosum. Nat Prod Commun 9(5):607–608
Malagnac F, Wendel B, Goyon C, Faugeron G, Zickler D, Rossignol JL, Noyer-Weidner M, Vollmayr P, Trautner TA, Walter J (1997) A gene essential for de novo methylation and development in Ascobolus reveals a novel type of eukaryotic DNA methyltransferase structure. Cell 91(2):281–290
Margeot A, Hahn-Hagerdal B, Edlund M, Slade R, Monot F (2009) New improvements for lignocellulosic ethanol. Curr Opin Biotechnol 20(3):372–380. doi:10.1016/j.copbio.2009.05.009
Marie-Nelly H, Marbouty M, Cournac A, Flot JF, Liti G, Parodi DP, Syan S, Guillén N, Margeot A, Zimmer C, Koszul R (2014) High-quality genome (re)assembly using chromosomal contact data. Nat Commun 5:5695. doi:10.1534/genetics.107
Martín J, García-Estrada C, Rumbero A, Recio E, Albillos SM, Ullán RV, Martín JF (2011) Characterization of an autoinducer of penicillin biosynthesis in Penicillium chrysogenum. Appl Environ Microbiol 77(16):5688–5696. doi:10.1128/AEM.00059-11
Martinez D, Berka RM, Henrissat B, Saloheimo M, Arvas M, Baker SE, Chapman J, Chertkov O, Coutinho PM, Cullen D, Danchin EG, Grigoriev IV, Harris P, Jackson M, Kubicek CP, Han CS, Ho I, Larrondo LF, de Leon AL, Magnuson JK, Merino S, Misra M, Nelson B, Putnam N, Robbertse B, Salamov AA, Schmoll M, Terry A, Thayer N, Westerholm-Parvinen A, Schoch CL, Yao J, Barabote R, Nelson MA, Detter C, Bruce D, Kuske CR, Xie G, Richardson P, Rokhsar DS, Lucas SM, Rubin EM, Dunn-Coleman N, Ward M, Brettin TS (2008) Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina). Nat Biotechnol 26(5):553–560. doi:10.1038/nbt1403
Meyers RA (2012) Epigenetic regulation and epigenomics. Wiley-Blackwell, Germany
Montanini B, Chen PY, Morselli M, Jaroszewicz A, Lopezm D, Martin F, Ottonello S, Pellegrini M (2014) Non-exhaustive DNA methylation-mediated transposon silencing in the black truffle genome, a complex fungal genome with massive repeat element content. Genome Biol 15(7):411. doi:10.1186/s13059-014-0411-5
Motorin Y, Lyko F, Helm M (2010) 5-methylcytosine in RNA: detection, enzymatic formation and biological functions. Nucleic Acids Res 38(5):1415–1430. doi:10.1093/nar/gkp1117
Nathan D, Ingvarsdottir K, Sterner DE, Bylebyl GR, Dokmanovic M, Dorsey JA, Whelan KA, Krsmanovic M, Lane WS, Meluh PB, Johnson ES, Berger SL (2006) Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev 20:966–976
Nicolás FE, de Haro JP, Torres-Martínez S, Ruiz-Vázquez RM (2007) Mutants defective in a Mucor circinelloides dicer-like gene are not compromised in siRNA silencing but display developmental defects. Fungal Genet Biol 44:504–516
Noma K, Allis CD, Grewal SI (2001) Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 293:1150–1155
Oda K, Kobayashi A, Ohashi S, Sano M (2011) Aspergillus oryzae laeA regulates kojic acid synthesis genes. Biosci Biotechnol Biochem 75(9):1832–1834
Patananan AN, Palmer JM, Garvey GS, Keller NP, Clarke SG (2013) A novel automethylation reaction in the Aspergillus nidulans LaeA protein generates S-methylmethionine. J Biol Chem 288(20):14032–14045. doi:10.1074/jbc.M113.465765
Proffitt JH, Davie JR, Swinton D, Hattman S (1984) 5-Methylcytosine is not detectable in Saccharomyces cerevisiae. DNA Mol Cell Biol 4:985–988
Ptak C, Petronis A (2008) Epigenetics and complex disease: from etiology to new therapeutics. Annu Rev Pharmacol Toxicol 48:257–276
Ramaiah M, Shum EY, Wilkinson MF (2012) How to activate a gene: decap its associated noncoding RNA. Mol Cell 45(3):271–273. doi:10.1016/j.molcel.2012.01.014
Rando OJ, Winston F (2012) Chromatin and transcription in yeast. Genetics 190(2):351–387. doi:10.1534/genetics.111.132266
Reik W, Dean W (2001) DNA methylation and mammalian epigenetics. Electrophoresis 2(14):2838–2843
Reyes-Dominguez Y, Bok JW, Berger H, Shwab EK, Basheer A, Gallmetzer A, Scazzocchio C, Keller N, Strauss J (2010) Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans. Mol Microbiol 76(6):1376–1386. doi:10.1111/j.1365-2958.2010.07051.x
Ries L, Pullan ST, Delmas S, Malla S, Blythe MJ, Archer DB (2013) Genome-wide transcriptional response of Trichoderma reesei to lignocellulose using RNA sequencing and comparison with Aspergillus niger. BMC Genomics 14:541. doi:10.1186/1471-2164-14-541
Robzyk K, Recht J, Osley MA (2000) Rad6-dependent ubiquitination of histone H2B in yeast. Science 287(5452):501–504
Rokem JS (2010) Industrial mycology. In: Doelle HW, Rokem S, Berovic M (eds) Biotechnology, Vol. 6. Encyclopedia of life support systems publishers, developed under the auspices of the UNESCO. Eolss Publishers, Paris, pp 75–97
Romano N, Macino G (1992) Quelling: transient inactivation of gene expression in Neurospora crassa by transformation with homologous sequences. Mol Microbiol 6:3343–3353
Sarikaya-Bayram Ö, Palmer JM, Keller NP, Braus GH, Bayram Ö (2015) One Juliet and four Romeos: VeA and its methyltransferases. Front Microbiol 6:1. doi:10.3389/fmicb.2015.00001
Schumacher J, Simon A, Cohrs KC, Traeger S, Porquier A, Dalmais B, Viaud M, Tudzynski B (2015) The VELVET complex in the gray mold fungus Botrytis cinerea: impact of BcLAE1 on differentiation, secondary metabolism and virulence. Mol Plant Microbe Interact. doi:10.1094/MPMI-12-14-0411-R
Seiboth B, Karimi Aghcheh R, Phatale PA, Linke R, 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. doi:10.1111/j.1365-2958.2012.08083.x
Selker EU (1990) Premeiotic instability of repeated sequences in Neurospora crassa. Annu Rev Genet 24:579–613
Selker EU, Cambareri EB, Jenson BC, Haack KR (1987) Rearrangement of duplicated DNA in specialized cells of Neurospora. Cell 51(5):741–752
Shaaban M, Palmer JM, El-Naggar WA, El-Sokkary MA, El Habib SE, Keller NP (2010) Involvement of transposon-like elements in penicillin gene cluster regulation. Fungal Genet Biol 47(5):423–432. doi:10.1016/j.fgb.2010.02.006
Sharma KK (2015) Fungal genome sequencing: basic biology to biotechnology. Crit Rev Biotechnol 27:1–17
Shiio Y, Eisenman RN (2003) Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci 100:13225–13230
Shiu PK, Raju NB, Zickler D, Metzenberg RL (2001) Meiotic silencing by unpaired DNA. Cell 107(7):905–916
Steigele S, Nieselt K (2005) Open reading frames provide a rich pool of potential natural antisense transcripts in fungal genomes. Nucleic Acids Res 33(16):5034–5044
Sterner DE, Berger SL (2000) Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64(2):435
Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403(6765):41–45
Suka N, Suka Y, Carmen AA, Wu J, Grunstein M (2001) Highly specific antibodies determine histone acetylation site usage in yeast heterochromatin and euchromatin. Mol Cell 8(2):473–479
Sun Y, Cheng JY (2002) Hydrolysis of lignocellulosic materials for ethanol production: a review. Bioresour Technol 83(1):1–11
Tamame M, Antequera F, Villanueva JR, Santos T (1983) High-frequency conversion to a ‘fluffy’ developmental phenotype in Aspergillus spp. by 5-azacytidine treatment: evidence for involvement of a single nuclear gene. Mol Cell Biol 3:2287–2297
Tamaru H, Selker EU (2001) A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414(6861):277–283
Tamaru H, Selker EU (2003) Synthesis of signals for de novo DNA methylation in Neurospora crassa. Mol Cell Biol 23:2379–2394
Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28(10):2731–2739. doi:10.1093/molbev/msr121
Tang Y, Gao XD, Wang Y, Yuan BF, Feng YQ (2012) Widespread existence of cytosine methylation in yeast DNA measured by gas chromatography/mass spectrometry. Anal Chem 84(16):7249–7255. doi:10.1021/ac301727c
Todd RB, Hynes MJ, Andrianopoulos A (2006) The Aspergillus nidulans rcoA gene is required for veA dependent sexual development. Genetics 174:1685–1688
Ullán RV, Godio RP, Teijeira F, Vaca I, García-Estrada C, Feltrer R, Kosalkova K, Martín JF (2008) RNA-silencing in Penicillium chrysogenum and Acremonium chrysogenum: validation studies using beta-lactam genes expression. J Microbiol Methods 75(2):209–218. doi:10.1016/j.mimet.2008.06.001
van den Berg MA (2011) Impact of the Penicillium chrysogenum genome on industrial production of metabolites. Appl Microbiol Biotechnol 92(1):45–53. doi:10.1007/s00253-011-3476-z
van den Berg MA, Albang R, Albermann K, Badger JH, Daran JM, Driessen AJ, Garcia-Estrada C, Fedorova ND, Harris DM, Heijne WH, Joardar V, Kiel JA, Kovalchuk A, Martín JF, Nierman WC, Nijland JG, Pronk JT, Roubos JA, van der Klei IJ, van Peij NN, Veenhuis M, von Döhren H, Wagner C, Wortman J, Bovenberg RA (2008) Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum. Nat Biotechnol 26(10):1161–1168. doi:10.1038/nbt.1498
Van Vu B, Pham KTM, Nakayashiki H (2013) Substrate-induced transcriptional activation of the MoCel7C cellulase gene is associated with methylation of histone H3 at lysine 4 in the rice blast fungus Magnaporthe oryzae. Appl Environ Microbiol 79(21):6823–6832. doi:10.1128/AEM.02082-13
Veiga T, Nijland JG, Driessen AJ, Bovenberg RA, Touw H, van den Berg MA, Pronk JT, Daran JM (2012) Impact of velvet complex on transcriptome and penicillin G production in glucose-limited chemostat cultures of a β-lactam high-producing Penicillium chrysogenum strain. OMICS 16(6):320–333. doi:10.1089/omi.2011.0153
Waddington CH (1942) The epigenotype. Endeavour 1:18–20
Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43(6):904–914. doi:10.1016/j.molcel.2011.08.018
Wang XJ, Gaasterland T, Chua NH (2005) Genome-wide prediction and identification of cis-natural antisense transcripts in Arabidopsis thaliana. Genome Biol 6:R30
Weber M, Schübeler D (2007) Genomic patterns of DNA methylation: targets and function of an epigenetic mark. Curr Opin Cell Biol 19(3):273–280
Wood A, Schneider J, Shilatifard A (2005) Crosstalking histones: implications for the regulation of gene expression and DNA repair. Biochem Cell Biol 83:460–467
Wu H, Zhang Y (2011) Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. Genes Dev 25(23):2436–2452. doi:10.1101/gad.179184.111
Wu C, Kim YS, Smith KM, Li W, Hood HM, Staben C, Selker EU, Sachs MS, Farman ML (2009) Characterization of chromosome ends in the filamentous fungus Neurospora crassa. Genetics 181(3):1129–1145. doi:10.1534/genetics.107.084392
Xin Q, Gong Y, Lv X, Chen G, Liu W (2013) Trichoderma reesei histone acetyltransferase Gcn5 regulates fungal growth, conidiation, and cellulase gene expression. Curr Microbiol 67(5):580–589. doi:10.1007/s00284-013-0396-4
Xu F, Zhang K, Grunstein M (2005) Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell 121(3):375–385
Xu Q, Singh A, Himmel ME (2009) Perspectives and new directions for the production of bioethanol using consolidated bioprocessing of lignocellulose. Curr Opin Biotechnol 20(3):364–371. doi:10.1016/j.copbio.2009.05.006
Yamada R, Yoshie T, Wakai S, Asai-Nakashima N, Okazaki F, Ogino C, Hisada H, Tsutsumi H, Hata Y, Kondo A (2014) Aspergillus oryzae-based cell factory for direct kojic acid production from cellulose. Microb Cell Factories 13:71. doi:10.1186/1475-2859-13-71
Yang K, Zhuang Z, Zhang F, Song F, Zhong H, Ran F, Yu S, Xu G, Lan F, Wang S (2014a) Inhibition of aflatoxin metabolism and growth of Aspergillus flavus in liquid culture by a DNA methylation inhibitor. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 31:1–10
Yang X, Huang L, Ruan XL (2014b) Epigenetic modifiers alter the secondary metabolite composition of a plant endophytic fungus, Pestalotiopsis crassiuscula obtained from the leaves of Fragaria chiloensis. J Asian Nat Prod Res 16(4):412–417. doi:10.1080/10286020.2014.881356
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 270:46–55
Zutz C, Gacek A, Sulyok M, Wagner M, Strauss J, Rychli K (2013) Small chemical chromatin effectors alter secondary metabolite production in Aspergillus clavatus. Toxins (Basel) 5(10):1723–1741
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The authors own data reviewed in this paper which were funded by projects P21666 and I1249 of the Austrian Science Foundation.
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Aghcheh, R.K., Kubicek, C.P. Epigenetics as an emerging tool for improvement of fungal strains used in biotechnology. Appl Microbiol Biotechnol 99, 6167–6181 (2015). https://doi.org/10.1007/s00253-015-6763-2
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DOI: https://doi.org/10.1007/s00253-015-6763-2