Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1 - and SIR -dependent transcriptional silencing

• Published in: Genes & development Vol. 17; no. 18; pp. 2245 - 2258
• Main Authors: De Las Peñas, Alejandro, Pan, Shih-Jung, Castaño, Irene, Alder, Jonathan, Cregg, Robert, Cormack, Brendan P.
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 15.09.2003
• Subjects: Candida glabrata; Candida glabrata - genetics; Candida glabrata - pathogenicity; EPA1 gene; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Silencing; Lectins - genetics; Lectins - metabolism; Multigene Family; Rap1 protein; Research Papers; Sir3 protein; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Virulence - genetics; Virulence - physiology
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.1121003

Candida glabrata is an important opportunistic pathogen causing both mucosal and bloodstream infections. C. glabrata is able to adhere avidly to mammalian cells, an interaction that depends on the Epa1p lectin. EPA1 is shown here to be a member of a larger family of highly related genes encoded in subtelomeric clusters. Subtelomeric clustering of large families of surface glycoprotein-encoding genes is a hallmark of several pathogens, including Plasmodium, Trypanosoma , and Pneumocystis . In these other pathogens, a single surface glycoprotein is expressed, whereas other genes in the family are transcriptionally silent. Similarly, whereas EPA1 is expressed in vitro, EPA2-5 are transcriptionally repressed. This repression is shown to be due to regional silencing of the subtelomeric loci. In Saccharomyces cerevisiae , subtelomeric silencing is initiated by Rap1p binding to the telomeric repeats and subsequent recruitment of the Sir complex by protein-protein interaction. We demonstrate here that silencing of the subtelomeric EPA loci also depends on functional Sir3p and Rap1p. This identification and analysis of the EPA gene family provides a compelling example in an ascomycete of chromatin-based silencing of natural subtelomeric genes and provides for the first time in a pathogen, molecular insight into the transcriptional silencing of large subtelomeric gene families.