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

• DOI: 10.1242/jcs.244863
• Publication Date: 2020-06-04T15:49:32Z
• Authors: Li Sun; Xiao-Min Liu; Wen-Zhu Li; Yuan-Yuan Yi; Xiangwei He; Yamei Wang; Quan-Wen Jin
• Keywords: 0303 health sciences; 03 medical and health sciences; Heterochromatin; Schizosaccharomyces; RNA Interference; HSP90 Heat-Shock Proteins; Schizosaccharomyces pombe Proteins; Chromatin Assembly and Disassembly

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 RNA-induced transcriptional silencing (RITS) and Argonaute siRNA chaperone (ARC) RNAi effector complexes, the RNAi-independent factor Fft3, the shelterin complex subunit Poz1 and the Snf2/HDAC-containing repressor complex (SHREC). Our ChIP data suggest that Hsp90 regulates the efficient recruitment of the methyltransferase/ubiquitin ligase complex CLRC by shelterin to chromosome ends and targeting of the 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 the 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.