Local and regional chromatin silencing in Candida glabrata: consequences for adhesion and the response to stress.
Candida glabrata is a fungal pathogen frequently found as a commensal in humans. To colonize and disseminate successfully in the mammalian host, C. glabrata must detect signals within the host and reprogram gene expression to respond appropriately to hostile environmental conditions. One of the layers of regulation of expression of many virulence-related genes (adhesin-encoding genes, genes involved in response to oxidative stress and xenobiotics) is achieved through epigenetic mechanisms. Local and regional silencing is mediated by the activity of two NAD(+)-dependent histone deacetylases, Hst1 and Sir2, respectively, repressing many virulence genes. Hst1 and Sir2 interact with different repressor complexes to achieve regional or local silencing. Sir2 can associate with Sir4, which is then recruited to the telomere by Rap1 and yKu. Deacetylation of the histone tails creates high affinity binding sites for new molecules of the Sir complex, thereby spreading the silent domain over >20 kb. Many of the adhesin-encoding EPA genes are subject to this regulation. Hst1 in turn associates with the Sum1-Rfm1 complex. Sum1 is a DNA-binding protein, which recognizes specific sites at individual promoters, recruiting Hst1 to specific genes involved in the response to oxidative stress and xenobiotics, which results in their repression.
['De Las Peñas|Alejandro|A|', 'Juárez-Cepeda|Jacqueline|J|', 'López-Fuentes|Eunice|E|', 'Briones-Martín-Del-Campo|Marcela|M|', 'Gutiérrez-Escobedo|Guadalupe|G|', 'Castaño|Irene|I|']
D000818:Animals D041221:Candida glabrata D002448:Cell Adhesion D002843:Chromatin D004268:DNA-Binding Proteins D044127:Epigenesis, Genetic D005656:Fungal Proteins D015966:Gene Expression Regulation, Fungal D006655:Histone Deacetylases D054884:Host-Pathogen Interactions D006801:Humans D060066:Protein Interaction Maps D013312:Stress, Physiological
Hst1 Sir2 telomeres Sirtuins subtelomeric region