title: A novel downstream regulatory element cooperates with the silencing machinery to repress EPA1 expression in Candida glabrata.
abstract: Candida glabrata, an opportunistic fungal pathogen, adheres to mammalian epithelial cells; adherence is mediated primarily by the Epa1 adhesin. EPA1 is a member of a large gene family of ≈ 23 paralogues, which encode putative adhesins. In this study, we address how EPA1 transcription is regulated. Our data show that EPA1 expression is subject to two distinct negative regulatory mechanisms. EPA1 transcription is repressed by subtelomeric silencing: the Sir complex (Sir2-Sir4), Rap1, Rif1, yKu70, and yKu80 are required for full repression. Activation of EPA1 occurs immediately after dilution of stationary phase (SP) cells into fresh media; however, transcription is rapidly repressed again, limiting expression to lag phase, just as the cells exit stationary phase. This repression following lag phase requires a cis-acting regulatory negative element (NE) located in the EPA1 3'-intergenic region and is independent of telomere proximity. Bioinformatic analysis shows that there are 10 copies of the NE-like sequence in the C. glabrata genome associated with other EPA genes as well as non-EPA genes.
authors.affiliation: IPICYT, División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, San Luis Potosí, 78216, México.
authors.forename: Verónica
authors.initials: V
authors.lastname: Gallegos-García
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Pan
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Juárez-Cepeda
authors.forename: Candy Y
authors.initials: CY
authors.lastname: Ramírez-Zavaleta
authors.forename: Marcela Briones
authors.initials: MB
authors.lastname: Martin-del-Campo
authors.forename: Verónica
authors.initials: V
authors.lastname: Martínez-Jiménez
authors.forename: Irene
authors.initials: I
authors.lastname: Castaño
authors.forename: Brendan
authors.initials: B
authors.lastname: Cormack
authors.forename: Alejandro
authors.initials: A
authors.lastname: De Las Peñas
mesh_terms: D041221:Candida glabrata / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D002874:Chromosome Mapping; D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008828:Microbiological Techniques; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D003470:Culture Media; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D037102:Lectins; D046912:Multiprotein Complexes; D012097:Repressor Proteins; D015534:Trans-Activators; C120505:epithelial adhesin 1, Candida glabrata; D006655:Histone Deacetylases