A role for the cohesin complex in subtelomeric gene silencing in Saccharomyces cerevisiae

Abstract

Chromatin is a dynamic structure which reorganizes to support numerous chromosomal processes. Various histone and non-histone proteins are involved in chromatin organization. One such group of non-histone proteins, known as SMC (Structural Maintenance of Chromosomes) proteins, plays a pivotal role in chromosome organization. SMC proteins are highly conserved in all three domains of life. The Saccharomyces cerevisiae genome codes for at least six SMC proteins, which along with non-SMC partners form three different complexes named as cohesin, condensin and the SMC5/6 complex. Cohesin is an evolutionary conserved multi-subunit protein complex involved in multiple chromosomal processes such as sister chromatid cohesion, chromosome condensation, regulation of gene expression, DNA replication and repair etc. Cohesin binds to the centromeres, at sites along the chromosome arms and subtelomeric regions. However, its role at the telomeres remains largely elusive. In budding yeast, telomeres exist in a heterochromatin-like structure and transcription within 20kb from telomeres is repressed, in part by the histone modifying SIR-complex, a phenomenon known as telomere position effect (TPE). Here, we report a role for cohesin in subtelomeric gene silencing that extends even beyond the zone of SIR binding. We find that TPE is impaired in the mutants defective in the cohesin complex. We also find that clusters of subtelomeric genes were preferentially de-repressed in the cohesin mutant, whereas SIR binding and associated histone modifications were largely unaffected. Interestingly, genetic interaction analysis revealed that cohesin mediated repression is independent of Sir proteins. Moreover, mutation in cohesin resulted in reduced telomere tethering to the nuclear envelope and increased telomere accessibility to ectopically expressed bacterial Dam methylase, indicating a defect in telomere organization. Cohesin undergoes various post-translational modifications such as acetylation, phosphorylation and sumoylation. Here, we ...