A SIR-independent role for cohesin in subtelomeric silencing and organization

Abstract

Cohesin is a key determinant of chromosome architecture due to its DNA binding and tethering ability. Cohesin binds near centromeres and chromosome arms and also close to telomeres, but its role near telomeres remains elusive. In budding yeast, transcription within 20 kb of telomeres is repressed, in part by the histone-modifying silent information regulator (SIR) complex. However, extensive subtelomeric repressed domains lie outside the SIR-binding region, but the mechanism of silencing in these regions remains poorly understood. Here, we report a role for cohesin in subtelomeric silencing that extends even beyond the zone of SIR binding. Clusters of subtelomeric genes were preferentially derepressed in a cohesin mutant, whereas SIR binding was unaltered. Genetic interactions with known telomere silencing factors indicate that cohesin operates independent of the SIR-mediated pathway for telomeric silencing. Mutant cells exhibited Mpk1dependent Sir3 hyperphosphorylation that contributes to subtelomeric derepression to a limited extent. Compaction of subtelomeric domains and tethering to the nuclear envelope were impaired in mutant cells. Our findings provide evidence for a unique SIR-independent mechanism of subtelomeric repression mediated by cohesin. cohesin | silencing | telomere | chromatin organization | transcriptome C hromatin is organized in a nonrandom orderly manner within the nucleus, and this organization affects its functions. The primary configuration of chromatin in the form of basic histone-containing nucleosome arrays is further reorganized by association with nonhistone proteins such as SMC (structural maintenance of chromosomes) proteins that bring about higher-order folding states by loop extrusion and compaction (1, 2). Cohesin is a key architectural chromosomal protein complex of the SMC family (3). Smc proteins are conserved, essential chromosomal structural proteins that engage in diverse chromosomal transactions (1,4). Cohesin consists of a heterodimer of Smc1 and Smc3, forming a V-shaped structure having coiled-coil arm regions attached to ATPbinding head domains bridged by Mcd1/Scc1 associated with Scc3/

DNA Repair in Space and Time: Safeguarding the Genome with the Cohesin Complex

“…In S. pombe , the Psc3 (Scc3 in budding yeast) cohesin subunit directly interacts with the heterochromatin protein Swi6, which ensures cohesin recruitment and cohesion establishment at centromeres but is also important to ensure the genomic integrity of the heterochromatic mating type locus [ 58 ]. Finally, cohesin is enriched in subtelomeric regions and is required for their transcriptional repression in both fission and budding yeast through mechanisms that remain to be deciphered [ 59 , 60 ]. How cohesin shapes these compacted regions and whether this influences gene expression or DNA repair remains an open question.…”

Substrates of the MAPK Slt2: Shaping Yeast Cell Integrity

“…Mutants affected in cohesin, a key architectural chromosomal protein complex, have been shown to display telomere silencing defects as well as Slt2-dependent Sir3 hyperphosphorylation. However, in this case, Slt2 activity contributed to derepression only to a very limited extent, suggesting the existence of a Sir-independent mode of repression mediated by cohesin [118]. Several studies with different organism models, including S. cerevisiae, have shown that sirtuins are linked to aging [119].…”

Cohesin contributes to transcriptional repression of stage‐specific genes in the human malaria parasite

“…In P. falciparum , the current genome‐wide chromosome conformation capture (Hi‐C) datasets do not provide evidence of typical enhancer‐promoter interactions found in other eukaryotes (Ay et al , 2014 ; Bunnik et al , 2019 ). Moreover, in S. cerevisiae , a cohesin mutant resulted in the de‐repression of genes located in subtelomeric regions, perhaps via disruption of local chromatin structure (Kothiwal & Laloraya, 2019 ). However, the invasion‐related genes affected by Pf SMC3 are scattered across the genome (Dataset EV21 ).…”