IPICYT, Instituto Potosino de Investigación Científica y Tecnológica, División de Biología Molecular, San Luis Potosí, SLP, 78216, México.
Genetics. 2012 Jan;190(1):101-11. doi: 10.1534/genetics.111.135251. Epub 2011 Nov 2.
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.
细胞黏附是条件致病真菌病原体光滑念珠菌致病性的重要步骤。这种黏附是由光滑念珠菌基因组中 EPA（上皮黏附素）基因家族的某些成员介导的。大多数 EPA 基因定位于光滑念珠菌的不同端粒附近，导致这些基因的转录通过染色质上的端粒旁沉默受到负调控。在体外，上皮细胞的黏附主要由 EPA1 介导，EPA1 是 EPA 家族中唯一在体外表达的成员。EPA1 在端粒 E(-R)的端粒旁区域与 EPA2 和 EPA3 形成簇。EPA2 和 EPA3 的沉默从这个端粒传播，这个过程依赖于 Sir2、-3、-4 和 Rif1 蛋白，但令人惊讶的是不依赖于 yKu70 和 yKu80 蛋白。在这里，我们描述了 yKu70/yKu80 不依赖的端粒 E(-R)沉默是由于位于 EPA3 和端粒之间的顺式作用原沉默子（Sil2126）的存在。当该元件放置在距离该端粒 31.9kb 处时，它可以沉默报告基因，但当它从端粒环境中去除时，或者当它放置在其他端粒附近或相对于报告基因倒置时，它不能沉默报告基因。重要的是，我们表明顺式作用的 Sil2126 元件是 yKu70/80 不依赖的这种端粒沉默所必需的，这强调了顺式元件对于某些 C. glabrata 端粒上抑制性染色质形成和扩展的重要性。
