Chromatin Loop Formation Induced by a Subtelomeric Protosilencer Represses Genes in .

Adherence, an important virulence factor, is mediated by the (Epithelial Adhesin) genes in the opportunistic pathogen Expression of adhesin-encoding genes requires tight regulation to respond to harsh environmental conditions within the host. The majority of genes are localized in subtelomeric regions regulated by subtelomeric silencing, which depends mainly on Rap1 and the Sir proteins. adhesion to epithelial cells is primarily mediated by Epa1. forms a cluster with and in the right telomere of chromosome E (E). This telomere contains a -acting regulatory element, the protosilencer Sil2126 between and the telomere. Interestingly, Sil2126 is only active in the context of its native telomere. Replacement of the intergenic regions between genes in E revealed that -acting elements between and are required for Sil2126 activity when placed 32 kb away from the telomere (Sil@-32kb). Sil2126 contains several putative binding sites for Rap1 and Abf1, and its activity depends on these proteins. Indeed, Sil2126 binds Rap1 and Abf1 at its native position and also when inserted at -32 kb, a silencing-free environment in the parental strain. In addition, we found that Sil@-32kb and Sil2126 at its native position can physically interact with the intergenic regions between and respectively, by chromosome conformation capture assays. We speculate that Rap1 and Abf1 bound to Sil2126 can recruit the Silent Information Regulator complex, and together mediate silencing in this region, probably through the formation of a chromatin loop.