Novel fungal transcriptional activators, Cmr1p of <i>Colletotrichum lagenarium</i> and Pig1p of <i>Magnaporthe grisea</i>, contain Cys2His2 zinc finger and Zn(II)2Cys6 binuclear cluster DNA‐binding motifs and regulate transcription of melanin biosynthesis genes in a developmentally specific manner

Tsuji, Gento; Kenmochi, Y.; Takano, Yoshitaka; Sweigard, James A.; Farrall, Leonard; Furusawa, Iwao; Horino, Osamu; Kubo, Yasuyuki

doi:10.1046/j.1365-2958.2000.02181.x

Cited by 152 publications

(133 citation statements)

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“…Infection of host plants by this fungus requires the production of melanin for successful invasion by formation of an infection structure called the appressorium (132). Cmr1p, a Zn(II) 2 Cys 6 protein, is a positive regulator of the expression of melanin biosynthetic structural genes SCD1 and THR1 in this species (266). ZFR1 is another example of a gene encoding a zinc cluster protein involved in secondary metabolite production.…”

Section: Zinc Cluster Proteins In Other Speciesmentioning

confidence: 99%

A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

MacPherson¹,

Larochelle²,

Turcotte

2006

Microbiol Mol Biol Rev

489

554

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SUMMARY The trace element zinc is required for proper functioning of a large number of proteins, including various enzymes. However, most zinc-containing proteins are transcription factors capable of binding DNA and are named zinc finger proteins. They form one of the largest families of transcriptional regulators and are categorized into various classes according to zinc-binding motifs. This review focuses on one class of zinc finger proteins called zinc cluster (or binuclear) proteins. Members of this family are exclusively fungal and possess the well-conserved motif CysX2CysX6CysX5-12CysX2CysX6-8Cys. The cysteine residues bind to two zinc atoms, which coordinate folding of the domain involved in DNA recognition. The first- and best-studied zinc cluster protein is Gal4p, a transcriptional activator of genes involved in the catabolism of galactose in the budding yeast Saccharomyces cerevisiae. Since the discovery of Gal4p, many other zinc cluster proteins have been characterized; they function in a wide range of processes, including primary and secondary metabolism and meiosis. Other roles include regulation of genes involved in the stress response as well as pleiotropic drug resistance, as demonstrated in budding yeast and in human fungal pathogens. With the number of characterized zinc cluster proteins growing rapidly, it is becoming more and more apparent that they are important regulators of fungal physiology.

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Section: Zinc Cluster Proteins In Other Speciesmentioning

confidence: 99%

A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

MacPherson¹,

Larochelle²,

Turcotte

2006

Microbiol Mol Biol Rev

489

554

View full text Add to dashboard Cite

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“…In Colletotrichum, melanization in mycelia and appressoria is controlled by different transcription factors (60). However, the A. fumigatus melanin cluster does not carry any regulatory factor (10,22), unlike some other fungi (61).…”

Section: Figmentioning

confidence: 99%

Laccases Involved in 1,8-Dihydroxynaphthalene Melanin Biosynthesis in Aspergillus fumigatus Are Regulated by Developmental Factors and Copper Homeostasis

2013

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Aspergillus fumigatus produces heavily melanized infectious conidia. The conidial melanin is associated with fungal virulence and resistance to various environmental stresses. This 1,8-dihydroxynaphthalene (DHN) melanin is synthesized by enzymes encoded in a gene cluster in A. fumigatus, including two laccases, Abr1 and Abr2. Although this gene cluster is not conserved in all aspergilli, laccases are critical for melanization in all species examined. Here we show that the expression of A. fumigatus laccases Abr1/2 is upregulated upon hyphal competency and drastically increased during conidiation. The Abr1 protein is localized at the surface of stalks and conidiophores, but not in young hyphae, consistent with the gene expression pattern and its predicted role. The induction of Abr1/2 upon hyphal competency is controlled by BrlA, the master regulator of conidiophore development, and is responsive to the copper level in the medium. We identified a developmentally regulated putative copper transporter, CtpA, and found that CtpA is critical for conidial melanization under copper-limiting conditions. Accordingly, disruption of CtpA enhanced the induction of abr1 and abr2, a response similar to that induced by copper starvation. Furthermore, nonpigmented ctpA⌬ conidia elicited much stronger immune responses from the infected invertebrate host Galleria mellonella than the pigmented ctpA⌬ or wild-type conidia. Such enhancement in eliciting Galleria immune responses was independent of the ctpA⌬ conidial viability, as previously observed for the DHN melanin mutants. Taken together, our findings indicate that both copper homeostasis and developmental regulators control melanin biosynthesis, which affects conidial surface properties that shape the interaction between this pathogen and its host.A spergillus fumigatus is an opportunistic pathogen that causes life-threatening invasive disease in immunocompromised hosts (1). Its asexual spores, named conidia, are the initial source of inocula for infection and are the vehicles for dispersal and survival. Under favorable conditions, conidia break dormancy and grow as elongated, highly polarized hyaline hyphae. Upon achieving competency and exposure to air, hyphae produce aerial conidiophore stalks and develop elaborate multicellular conidiophores that generate chains of melanized uninucleate conidia (2, 3) (Fig. 1A and B). BrlA, a C 2 H 2 zinc finger transcription factor, is the master regulator that controls the initiation of conidiophore development in Aspergillus (4, 5). AbaA and WetA, two other important regulators that function downstream of BrlA, are required for proper progression of conidiation (6). The abaA gene is activated during the middle stage of conidiophore development, while the wetA gene is required for the activation of late conidiation-specific genes.The 1,8-dihydroxynaphthalene (DHN) melanin coating A. fumigatus conidia gives them their characteristic bluish green color (Fig. 1B). Melanin is an amorphous polymer that is produced by a variety of microbes and ...

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“…Such genes regulate multiple physiological processes and generally respond to environmental cues such as pH, temperature, and nutrition (27,45). Regulation of many clustered genes is also largely dependent on pathway-specific transcription (18,22,42) and signal transduction pathways that link secondary metabolism with sporulation (13).LaeA is a global regulator of SM in the aspergilli. LaeA, a putative methyltransferase, was first identified in Aspergillus nidulans (5), A. fumigatus (6), and, subsequently, A. flavus (25).…”

mentioning

confidence: 99%

Suppressor Mutagenesis Identifies a Velvet Complex Remediator of Aspergillus nidulans Secondary Metabolism

et al. 2010

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Fungal secondary metabolites (SM) are bioactive compounds that are important in fungal ecology and, moreover, both harmful and useful in human endeavors (e.g., as toxins and pharmaceuticals). Recently a nuclear heterocomplex termed the Velvet complex, characterized in the model ascomycete Aspergillus nidulans, was found to be critical for SM production. Deletion of two members of the Velvet complex, laeA and veA, results in near loss of SM and defective sexual spore production in A. nidulans and other species. Using a multicopy-suppressor genetics approach, we have isolated an Aspergillus nidulans gene named rsmA (remediation of secondary metabolism) based upon its ability to remediate secondary metabolism in ⌬laeA and ⌬veA backgrounds. Overexpression of rsmA (OE::rsmA) restores production of sterigmatocystin (ST) (a carcinogenic SM) via transcriptional activation of ST biosynthetic genes. However, defects in sexual reproduction in either ⌬laeA or ⌬veA strains cannot be overcome by OE::rsmA. An intact Velvet complex coupled with an OE::rsmA allele increases SM many fold over the wild-type level, but loss of rsmA does not decrease SM. RsmA encodes a putative bZIP basic leucine zipper-type transcription factor.Secondary metabolites are biologically active compounds that are diverse in structure and often possess either pharmacological or toxic properties. To customize and control the biosynthesis of these natural products, we must understand how secondary metabolites (SM) are regulated. In fungi, SM production is controlled by global transcription factors encoded by genes unlinked to the SM biosynthetic gene clusters. Such genes regulate multiple physiological processes and generally respond to environmental cues such as pH, temperature, and nutrition (27,45). Regulation of many clustered genes is also largely dependent on pathway-specific transcription (18,22,42) and signal transduction pathways that link secondary metabolism with sporulation (13).LaeA is a global regulator of SM in the aspergilli. LaeA, a putative methyltransferase, was first identified in Aspergillus nidulans (5), A. fumigatus (6), and, subsequently, A. flavus (25). Overexpression (OE) of laeA increases the production of multiple metabolites in the aspergilli, whereas deletion of laeA silences expression of SM genes (1,5,8,20). LaeA is thus used as a genomic mining tool, providing a novel method for identifying new SM through microarray and chemical analyses (8,20,34). Moreover, deletion of laeA in A. fumigatus decreases the virulence of this human pathogen (4, 6); similarly, A. flavus laeA deletants are also reduced in virulence on host seed (1, 25). LaeA homologs are also found in other filamentous fungi such as Penicillium chrysogenum and Fusarium fujikuroi, where they control SM, pigmentation, sporulation, and virulence (29,43).Another important SM regulatory protein identified in A. nidulans is encoded by veA, otherwise known as velvet. VeA is a light-dependent regulator governing both development and SM production in several aspergilli (A...

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Novel fungal transcriptional activators, Cmr1p of Colletotrichum lagenarium and Pig1p of Magnaporthe grisea, contain Cys2His2 zinc finger and Zn(II)2Cys6 binuclear cluster DNA‐binding motifs and regulate transcription of melanin biosynthesis genes in a developmentally specific manner

Cited by 152 publications

References 56 publications

A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

Laccases Involved in 1,8-Dihydroxynaphthalene Melanin Biosynthesis in Aspergillus fumigatus Are Regulated by Developmental Factors and Copper Homeostasis

Suppressor Mutagenesis Identifies a Velvet Complex Remediator of Aspergillus nidulans Secondary Metabolism

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