Tadeo X, Wang J, Kallgren SP, Liu J, Reddy BD, Qiao F, Jia S

Genes Dev. Cold Spring Harbor Lab; 2013 Nov 15;27(22):2489–99


The RNAi pathway is required for heterochromatin assembly at repetitive DNA elements in diverse organisms. In fission yeast, loss of RNAi causespericentric heterochromatin defects, compromising gene silencing and chromosome segregation. Here we show that deletion of telomere shelterincomponents restores pericentric heterochromatin and its functions in RNAi mutants. We further isolated a separation-of-function mutant of Poz1 and revealed that defective telomere silencing, but not telomere length control, is critical for bypassing RNAi. Further analyses demonstrated that compromising shelterin-mediated heterochromatin assembly in RNAi mutants releases heterochromatin protein Swi6, which is redistributed topericentric regions through RNAi-independent heterochromatin assembly pathways. Given the high mobility of Swi6 protein and that increased levels of Swi6 facilitates heterochromatin spreading as well as ectopic heterochromatin assembly, our results suggest that constitutive heterochromatindomains use multiple pathways to form high-affinity platforms to restrain Swi6, thus limiting its availability and avoiding promiscuous heterochromatinformation.