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Chapter 4 : Mating-Type Locus Control of Cell Identity
Category: Fungi and Fungal Pathogenesis
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This chapter addresses how MAT loci is identified from budding ascomycetes to filamentous ascomycetes to basidiomycetes function to specify cell identity. The chapter begins with an introduction to the cell identity determination paradigm established in the budding yeast Saccharomyces cerevisiae. It explores how cell identity determination affects sexual reproduction in basidiomycetes. Through these examples, we see how cell identity determination lays the foundation for effective sexual reproduction and survival across diverse fungi. In S. cerevisiae, a single-celled ascomycete, growth can take place either clonally through haploid cell budding, or sexually through mating followed by meiosis. For most ascomycetes, the precise mechanisms by which these transcriptional regulators specify cell identity is not known; however, MAT control in S. pombe is explored in more detail. An ascomycete in which cell identity determination has been studied in detail is the human fungal pathogen Candida albicans. A detailed expression analysis determined the transcriptional profiles of cells with targeted deletions of the MTL regulator components in every possible combination in both the white and opaque phases. Control of cell identity by the MAT locus in basidiomycetes expands the simple transcription factor-encoding locus seen in ascomycetes to a more complex structure. The fate of fused hyphae is determined by the interactions of the homeodomain proteins after cell fusion: if different alleles of an homeodomain (HD1) and HD2 protein from the same gene pair interact, this complex will form a heterodimeric transcriptional regulator that stimulates dikaryotic growth.
Key Concept Ranking
- Restriction Fragment Length Polymorphism
MAT control of cell identity in S. cerevisiae. (A) In S. cerevisiae, MATa in a cells encodes the homeodomain transcription factor a1. MATα in α cells encodes the α-domain protein α1 and the homeodomain transcription factor α2. In diploid cells, both MATa and MATα alleles are present. (B) In a cells, the a1 protein is present but has no known function. The a-specific genes (asg) are constitutively expressed, whereas the α-specific genes (αsg) are not expressed. In α cells, α2 represses a-specific genes while α1 activates α-specific genes to specify the α cell type. In an a/α diploid, α2 maintains repression of a-specific genes, but it also heterodimerizes with a1 to form a transcriptional regulatory complex that represses haploid-specific genes (including α1). This repression establishes the diploid cell type, allowing continued sexual development.
MAT control of cell identity in S. pombe. (A) The MAT locus of S. pombe contains two alleles that specify the P or M cell type. Haploid P cells contain the mat1-P allele that encodes mat1-Pc (homeodomain) and mat1-Pm (α domain) proteins. The mat1-M allele is contained within M cells and encodes the mat1-Mc (HMG domain) and mat1-Mm (unknown domain) proteins. All of the MAT proteins are required for sexual development. (B) In haploid cells, Pc or Mc is expressed constitutively to specify the P or M cell identity, respectively. In diploid P/M cells, all four MAT proteins are expressed. Mc and Pm are thought to bind to the mei3 promoter to activate its expression (the product of which is a direct inducer of meiosis).
MAT control of cell identity in C. albicans. (A) The mating-type-like (MTL) locus of C. albicans has two alleles, each housing transcription factors and three other kinds of genes. MTLa contains the homeodomain transcription factor a1 and the HMG-domain protein a2. MTLα encodes the α-domain protein α1 and the homeodomain transcription factor α2. In addition to these proteins, both MTLa and MTLα encode diverged alleles of a poly(A) polymerase (PAP), an oxysterol binding protein (OBP), and a phosphatidyl inositol kinase (PIK). The roles of PAP, OBP, and PIK in cell type determination are unknown. (B) Cells that contain only a information (a/a or a/Δ at the MTL locus) mate as a cells because the putative transcription factor a2 activates genes involved in establishing the a-type mating. Cells that contain only α information (α/α or α/Δ at the MTL locus) mate as α cells because the predicted transcription factor α1 activates genes involved in α-type mating. Cells containing both a and α information (a/α at the MTL locus) do not mate with other cells because a1 and α2 work together to repress genes that are necessary for mating and white-opaque switching. Cells that are unable to switch from white to opaque cannot undergo mating, and a1 and α2 repress this switch.
MAT configurations in filamentous ascomycetes. (A) The mating-type (MAT) locus of C. heterostrophus has two alleles: MAT1-1 encodes the α-domain protein MAT1-1-1, and MAT1-2 encodes the HMG-domain protein MAT1-2-1. (B) The mat+ allele of P. anserina encodes the HMG-domain protein FPR1. The mat− allele encodes the HMG-domain protein SMR2, a protein of unknown class, SMR1, and the α-domain protein FMR1. (C) The mat a allele of N. crassa encodes the HMG-domain protein MAT a-1 and a protein of unknown class, MAT a-2. The mat A allele encodes the HMG-domain protein MAT A-3, a protein of unknown class, MAT A-2, and the α-domain protein MAT A-1.
MAT control of cell and nuclear identity in P. anserina. (A) Fertilization occurs between opposite mating types when a male structure fuses with a female structure and the male nucleus is transferred. In these cells, mating type (either mat+ or mat−) is specified by the expression of mating-type-specific proteins: FMR1 is expressed in mat+ cells, and FPR1 is expressed in mat− cells. (B) After fertilization and repeated mitotic divisions, a plurinucleate cell results. The nuclei from this cell must be paired and sequestered to a dikaryotic cell that contains one nucleus of each mating type. The mat+ nuclear identity is specified by the FPR1 protein, and the mat− nuclear identity is specified by the FMR1 and SMR2 proteins.
MAT control of cell identity in U. maydis. (A) The a1 MAT allele houses the cell-type-specific pheromone gene mfa1 and pheromone receptor gene pra1. a2 contains their counterparts, mfa2 and pra2, as well as lga2 and rga2. The products of lga2 and rga2 do not belong to any known class of proteins and have no obvious role in sexual development but have been found to be involved in mitochondrial function ( 8 ). The b locus encodes two homeodomain transcription factors, bE and bW, with bE1 and bW1 housed in the b1 allele and bE2 and bW2 housed in the b2 allele. (B) Haploid cell types (large, open circles) are specified by the expression of the pheromone mfa1 (•) and pheromone receptor pra1 (forked receptor on the cell surface) or the pheromone mfa2 (▪) and pheromone receptor pra2 (semicircular receptor on cell surface). Pheromones are sensed by their corresponding receptors on the opposite cell type. These signals activate cell fusion when two cells of opposite mating types encounter one another. After cell fusion, the proteins encoded by the b locus (bE and bW) interact with one another in specific combinations to specify the dikaryotic state and prepare cells for further sexual development.
MAT control of cell identity in C. cinerea. (A) The A locus contains four pairs of divergently transcribed genes that each encode two homeodomain transcription factors, HD1 and HD2. The a pair is contained within the α sublocus, while the β sublocus contains the b and d pairs. (These pairs are not always complete and sometimes encode only one of the two genes.) Lettering within the gene name refers to the gene pair from which it originated, while the number indicates the type of homeodomain it represents (1 for HD1 and 2 for HD2). The B locus contains three subfamilies of genes. Each subfamily has two genes encoding pheromones (phb) and one gene encoding a pheromone receptor (rcb). The pheromone products of one subfamily are proposed to interact with the pheromone receptor of an allelic subfamily. (B) The products of both the A and B mating-type loci act to initiate and maintain the dikaryotic state. The filamentous dikaryon contains one nucleus from each mating type in each cell and characteristic clamp connections (domed structures between adjacent filament cells). The products of the B locus (pheromones and pheromone receptors) control nuclear migration and clamp cell fusion, while the products of the A locus (HD1 and HD2 homeodomain proteins) control the expression of genes required to drive dikaryon formation, specifically to coordinate nuclear division and initiate clamp cell formation.
MAT control of cell identity in C. neoformans. (A) The mating-type (MAT) locus of C. neoformans contains pheromones, pheromone receptors, and homeodomain transcription factors as well as many genes with no apparent role in cell type determination. A schematic of the MAT locus for C. neoformans var. neoformans is shown. MATa encodes three copies of the MFa pheromone, the putative pheromone receptor Ste3a, and the homeodomain transcription factor Sxi2a. MATα encodes three copies of the MFα pheromone, the putative pheromone receptor Ste3α, and the homeodomain transcription factor Sxi1α. The remaining genes have related but diverged alleles in both MATa and MATα. Note: schematic diagram is not to scale. (B) The determinants of haploid cell identity are unknown; however, it is likely that pheromones and pheromone receptors play a role. The expression of MFa could specify the a mating type, and the expression of MFα could specify the α mating type. Pheromones would be sensed by surface receptors of opposite mating types to activate cell fusion when two cells of opposite mating types are in close proximity to one another. After cell fusion has taken place, the homeodomain transcription factors Sxi1α and Sxi2a are predicted to interact with one another to activate the expression of genes involved in the specification of the dikaryotic state. The dikaryon is then capable of undergoing further sexual development.