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Clr4SUV39H1 ubiquitination and non-coding RNA mediate transcriptional silencing of heterochromatin via Swi6 phase separation

Author

Listed:
  • Hyun-Soo Kim

    (Cold Spring Harbor
    Cold Spring Harbor)

  • Benjamin Roche

    (Cold Spring Harbor
    School of Medicine & Health Sciences)

  • Sonali Bhattacharjee

    (Cold Spring Harbor)

  • Leila Todeschini

    (University of Grenoble Alpes)

  • An-Yun Chang

    (Cold Spring Harbor)

  • Christopher Hammell

    (Cold Spring Harbor)

  • André Verdel

    (University of Grenoble Alpes)

  • Robert A. Martienssen

    (Cold Spring Harbor
    Cold Spring Harbor)

Abstract

Transcriptional silencing by RNAi paradoxically relies on transcription, but how the transition from transcription to silencing is achieved has remained unclear. The Cryptic Loci Regulator complex (CLRC) in Schizosaccharomyces pombe is a cullin-ring E3 ligase required for silencing that is recruited by RNAi. We found that the E2 ubiquitin conjugating enzyme Ubc4 interacts with CLRC and mono-ubiquitinates the histone H3K9 methyltransferase Clr4SUV39H1, promoting the transition from co-transcriptional gene silencing (H3K9me2) to transcriptional gene silencing (H3K9me3). Ubiquitination of Clr4 occurs in an intrinsically disordered region (Clr4IDR), which undergoes liquid droplet formation in vitro, along with Swi6HP1 the effector of transcriptional gene silencing. Our data suggests that phase separation is exquisitely sensitive to non-coding RNA (ncRNA) which promotes self-association of Clr4, chromatin association, and di-, but not tri- methylation instead. Ubc4-CLRC also targets the transcriptional co-activator Bdf2BRD4, down-regulating centromeric transcription and small RNA (sRNA) production. The deubiquitinase Ubp3 counteracts both activities.

Suggested Citation

  • Hyun-Soo Kim & Benjamin Roche & Sonali Bhattacharjee & Leila Todeschini & An-Yun Chang & Christopher Hammell & André Verdel & Robert A. Martienssen, 2024. "Clr4SUV39H1 ubiquitination and non-coding RNA mediate transcriptional silencing of heterochromatin via Swi6 phase separation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53417-9
    DOI: 10.1038/s41467-024-53417-9
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