[en] Epigenetic modifications, such as acetylation, phosphorylation, methylation, ubiquitination, and ADP ribosylation, of the highly conserved core histones, H2A, H2B, H3, and H4, influence the genetic potential of DNA. The enormous regulatory potential of histone modification is illustrated in the vast array of epigenetic markers found throughout the genome. The histone acetylation level is balanced by histone acetyltrasferases (HAT) and histone deacetylases (HDAC). The human fungal pathogen, Candida albicans can grow in at least four different morphologies: yeast, pseudohyphae, hyphae and chlamydospore. Pseudohyphae and hyphae are both elongated and sometimes there has been little attempt to distinguish between them, as both are "filamentous forms" of the fungus. The switch between these forms is the result of a complex interplay of external and internal factors and is coordinated in part by polarity-regulating proteins that are conserved among eukaryotic cells. C. albicans uses a network of multiple signaling pathways to control the yeast-->hypha transition. These pathways control the transcription of a common set of hypha-specific genes, many of which encode known virulence factors. Efg1p is the mayor regulator of morphogenesis in C. albicans. Sin3p, a component of a specific histone deacetylase complex Sin3p-Rpd3p in S. cerevisiae, was shown to bind to the EFG1 promoter. A proposed model explains the relationship between Efg1p-Sin3p and HDAC in morphogenesis. C. albicans has at least five HDACs. The focus of our work was on understanding the role of two of them, Hos3p and Rpd3p in the regulation of the morphogenesis in the pathogen yeast C. albicans.In this work, we have disrupted three genes which codified to Hos3p and Rpd3p (two of them) in C. albicans and have analyzed their role in morphogenesis and especially in the yeast-hypha transition.Cells lacking of HOS3 gene could grow normally on solid or in liquid media, even during the yeast-hypha transition. ?hos3 cells were able to form normal chlamydospores. We have analyzed global transcription profile and we obtained 233 differentially expressed genes after comparison of the hos3 mutant with the C. albicans wild type strain. These genes belong to several functional categories mainly those involved in metabolism, cellular transport and cellular communication/signal transduction. C. albicans has two genes homologous to ScRpd3p. We have disrupted both genes and the double mutant showed an altered behaviour during the dimorphic switch and chlamydospores formation. Single mutants presented wild type phenotype. The double mutant has also altered the expression of EFG1, CPH1, YWP1 and HWP1, genes implicated in morphogenesis.

[es] Las modificaciones epigen?ticas tales como acetilaci?n, fosforilaci?n, ubiquitinaci?n y ADP-ribosilaci?n de las histonas influyen en la gen?tica potencial del DNA. El nivel de acetilaci?n de las histonas est? controlado por las acetilatransferasas de histonas (HAT) y las Desacetilasas de histonas (HDAC). El pat?geno humano Candida albicans puede crecer en al menos cuatro diferentes morfolog?as: levaduras, pseudohifas, hifas y clamidosporas. Las pseudohifas y las hifas son formas elongadas y se engloban bajo la denominaci?n de formas filamentosas. El cambio entre todas las morfolog?as es resultado de compleja interacci?n entre factores internos y externos y est? coordinado in parte por prote?nas que regulan polaridad y que est?n conservadas en las c?lulas eucariotas. En C. albicans existen m?ltiples rutas de regulaci?n que controlan la transici?n levadura-hifa. Estas rutas controlan la transcripci?n de un set de genes espec?ficos de hifa, la mayor?a de ellos codifican conocidos factores de virulencia. Efg1p es el mayor regulador morfogen?tico de C. albicans. Sin3p, un componente del complejo multiproteico de Desacetilasas de histonas Sin3p-Rpd3p en Saccharomyces cerevisiae, se une al promotor del gen EFG1. Con todos los datos obtenidos se propuso un modelo que explica la relaci?n entre Efg1p-Sin3p y las HDAC en la morfog?nesis de C. albicans. En esta levadura existen al menos cinco HDACs. El objetivo de este trabajo fue entender el papel de dos de ellas, Hos3p y Rpd3p en la regulaci?n de la morfog?nesis de la levadura pat?gena C. albicans.En este trabajo, se interrumpieron tres genes que codifican las prote?nas Hos3p y Rpd3p (dos de ellos) en C. albicans y se analiz? el papel de los mismos en la morfog?nesis, en especial en la transici?n levadura-hifa.Las c?lulas carentes del gen HOS3 mostraron una morfolog?a similar a la del silvestre tanto en medio s?lido como en medio l?quido, incluso durante la transici?n dim?rfica. Tambi?n fueron capaces de formar clamidosporas. Se analiz? el perfil global de transcripci?n y se obtuvieron 233 genes cuya expresi?n se ve?a afectada por la interrupci?n del gen HOS3 tras la comparaci?n del mutante ?hos3 y la cepa silvestre. Estos genes pertenec?an a diferentes categor?as funcionales, principalmente metabolismo, transporte celular y comunicaci?n celular y transducci?n de la se?al.C. albicans tiene dos genes hom?logos al gen que codifica la HDAC Rpd3p en S. cerevisiae. Ambos genes fueron interrumpidos y el doble mutante presentaba alteraciones en la transici?n levadura-hifa y la formaci?n de clamidosporas. Los mutantes sencillos presentaron fenotipo similar a la cepa silvestre. El doble mutante adem?s present? alterada la expresi?n de los genes implicados en el cambio dim?rfico EFG1, CPH1, YWP1 y HWP.