Methylation and demethylation activities of a C. elegans MLL-like complex attenuate RAS signalling

Kate Fisher, Stacey M. Southall, Jon R. Wilson, Gino B. Poulin

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The conserved Mixed Lineage Leukaemia (MLL) complex deposits activating methyl marks on histone tails through a methyltransferase (MT) activity. Here we provide in vivo evidence that in addition to methylation, the C. elegans MLL-like complex can remove specific methyl marks linked to repression of transcription. This supports the proposed model in which the MLL complex orchestrates both the deposition and the removal of methyl marks to activate transcription. We have uncovered the MLL-like complex in a large-scale RNAi screen designed to identify attenuators of RAS signalling during vulval development. We have also found that the histone acetyltransferase complex, NuA4/TIP60, cooperates with the C. elegans MLL-like complex in the attenuation of RAS signalling. Critically, we show that both complexes regulate a common novel target and attenuator of RAS signalling, AJM-1 (Apical Junction Molecule-1). Therefore, the C. elegans MLL-like complex cooperates with the NuA4/TIP60 complex to regulate the expression of a novel effector, AJM-1. © 2010 Elsevier Inc.
    Original languageEnglish
    Pages (from-to)142-153
    Number of pages11
    JournalDevelopmental Biology
    Volume341
    Issue number1
    DOIs
    Publication statusPublished - May 2010

    Keywords

    • C. elegans
    • Chromatin
    • EGFR signalling
    • RAS
    • Transcription
    • Vulva development
    • Vulval development

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