Molecular chaperone Hsp90 regulates heterochromatin assembly through stabilizing multiple complexes in fission yeast

Abstract

In the fission yeast Schizosaccharomyces pombe, both RNAi machinery and RNAi- independent factors mediate transcriptional and posttranscriptional silencing and heterochromatin formation. Here, we show that the silencing of reporter genes at major native heterochromatic loci (centromeres, telomeres, mating-type locus and rDNA regions) and an artificially induced heterochromatin locus is alleviated in a fission yeast hsp90 mutant, hsp90-G84C. Also, H3K9me2 enrichment at heterochromatin regions, especially at the mating-type locus and subtelomeres, is compromised, suggesting heterochromatin assembly defects. We further discovered that Hsp90 is required for stabilization or assembly of the RNAi effector complexes RITS and ARC, RNAi-independent factor Fft3, shelterin complex subunit Poz1 and SHREC. Our ChIP data suggest that Hsp90 regulates the efficient recruitment of CLRC by shelterin to chromosome ends and targeting of SHREC and Fft3 to mating type locus and/or rDNA region. Finally, our genetic analyses demonstrated that increased heterochromatin spreading restores silencing at subtelomeres in hsp90-G84C mutant. Thus, this work uncovers a conserved factor critical for promoting RNAi-dependent and -independent heterochromatin assembly and gene silencing through stabilizing multiple effectors and effector complexes.