title: Methylation and demethylation activities of a C. elegans MLL-like complex attenuate RAS signalling.
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.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Fisher
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Southall
authors.forename: Jon R
authors.initials: JR
authors.lastname: Wilson
authors.forename: Gino B
authors.initials: GB
authors.lastname: Poulin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051548:Histone Acetyltransferases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D020703:ras GTPase-Activating Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
chemical_list: C441580:AJM-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C108739:GAP-1 protein, C elegans; D009687:Nuclear Proteins; C449640:SET-2 protein, C elegans; D020703:ras GTPase-Activating Proteins; C066646:let-60 protein, C elegans; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; D020794:Receptor Protein-Tyrosine Kinases; D018631:ras Proteins