Stc1: A Critical Link between RNAi and Chromatin Modification Required for Heterochromatin Integrity

Elizabeth H. Bayne, Sharon A. White, Alexander Kagansky, Dominika A. Bijos, Luis Sanchez-Pulido, Kwang-Lae Hoe, Dong-Uk Kim, Han-Oh Park, Chris P. Ponting, Juri Rappsilber, Robin C. Allshire

    Research output: Contribution to journalArticlepeer-review

    136 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)666-677
    Number of pages12
    JournalCell
    Volume140
    Issue number5
    DOIs
    Publication statusPublished - 5 Mar 2010

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