A Protosilencer of Subtelomeric Gene Expression in Candida glabrata with Unique Properties

Abstract

Adherence to host cells is an important step in the pathogenicity of the opportunistic fungal pathogen Candida glabrata. This adherence is mediated by some members of the large family of cell wall proteins encoded by the EPA (Epithelial Adhesin) genes present in the C. glabrata genome. The majority of the EPA genes are localized close to different telomeres in C. glabrata, resulting in a negative regulation of transcription of these genes through chromatin-based subtelomeric silencing. In vitro, adherence to epithelial cells is mainly mediated by Epa1, the only member of the EPA family that is expressed in vitro. EPA1 forms a cluster with EPA2 and EPA3 at the subtelomeric region of telomere E(-R). EPA2 and EPA3 are subject to silencing that propagates from this telomere in a process that depends on the Sir2, -3, -4, and Rif1 proteins, but surprisingly not on the yKu70 and yKu80 proteins. Here we describe that the yKu70/yKu80-independent silencing of telomere E(-R) is due to the presence of a cis-acting protosilencer (Sil2126) located between EPA3 and the telomere. This element can silence a reporter gene when placed 31.9 kb away from this telomere, but not when it is removed from the telomere context, or when it is placed near other telomeres, or inverted with respect to the reporter. Importantly, we show that the cis-acting Sil2126 element is required for the yKu70/80-independent silencing of this telomere, underscoring the importance of cis-elements for repressive chromatin formation and spreading on some telomeres in C. glabrata.