title: Stc1: a critical link between RNAi and chromatin modification required for heterochromatin integrity.
abstract: In fission yeast, RNAi directs heterochromatin formation at centromeres, telomeres, and the mating type locus. Noncoding RNAs transcribed from repeat elements generate siRNAs that are incorporated into the Argonaute-containing RITS complex and direct it to nascent homologous transcripts. This leads to recruitment of the CLRC complex, including the histone methyltransferase Clr4, promoting H3K9 methylation and heterochromatin formation. A key question is what mediates the recruitment of Clr4/CLRC to transcript-bound RITS. We have identified a LIM domain protein, Stc1, that is required for centromeric heterochromatin integrity. Our analyses show that Stc1 is specifically required to establish H3K9 methylation via RNAi, and interacts both with the RNAi effector Ago1, and with the chromatin-modifying CLRC complex. Moreover, tethering Stc1 to a euchromatic locus is sufficient to induce silencing and heterochromatin formation independently of RNAi. We conclude that Stc1 associates with RITS on centromeric transcripts and recruits CLRC, thereby coupling RNAi to chromatin modification.
authors.affiliation: Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Bayne
authors.forename: Sharon A
authors.initials: SA
authors.lastname: White
authors.forename: Alexander
authors.initials: A
authors.lastname: Kagansky
authors.forename: Dominika A
authors.initials: DA
authors.lastname: Bijos
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez-Pulido
authors.forename: Kwang-Lae
authors.initials: KL
authors.lastname: Hoe
authors.forename: Dong-Uk
authors.initials: DU
authors.lastname: Kim
authors.forename: Han-Oh
authors.initials: HO
authors.lastname: Park
authors.forename: Chris P
authors.initials: CP
authors.lastname: Ponting
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.forename: Robin C
authors.initials: RC
authors.lastname: Allshire
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D006570:Heterochromatin / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D008780:Methyltransferases / Q000235:genetics; D034622:RNA Interference; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D006570:Heterochromatin; D029702:Schizosaccharomyces pombe Proteins; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C112744:clr4 protein, S pombe