Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly.
The RNAi pathway is required for heterochromatin assembly at repetitive DNA elements in diverse organisms. In fission yeast, loss of RNAi causes pericentric heterochromatin defects, compromising gene silencing and chromosome segregation. Here we show that deletion of telomere shelterin components 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 to pericentric 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 heterochromatin domains use multiple pathways to form high-affinity platforms to restrain Swi6, thus limiting its availability and avoiding promiscuous heterochromatin formation.
Department of Biological Sciences, Columbia University, New York, New York 10027, USA;
Xavier
X
Tadeo
Jiyong
J
Wang
Scott P
SP
Kallgren
Jinqiang
J
Liu
Bharat D
BD
Reddy
Feng
F
Qiao
Songtao
S
Jia
D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D006570:Heterochromatin / Q000378:metabolism*; D009154:Mutation; D034622:RNA Interference; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; C529645:Poz1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C465958:Swi6 protein, S pombe; D034501:Telomere-Binding Proteins
RNAi; centromere; heterochromatin assembly; shelterin; telomere