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PMID:20188723

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Citation

Fisher, K, Southall, SM, Wilson, JR and Poulin, GB (2010) Methylation and demethylation activities of a C. elegans MLL-like complex attenuate RAS signalling. Dev. Biol. 341:142-53

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.

Links

PubMed Online version:10.1016/j.ydbio.2010.02.023

Keywords

Amino Acid Sequence; Animals; Caenorhabditis elegans/embryology; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/metabolism; Female; Gene Expression Regulation, Developmental; Histone Acetyltransferases/metabolism; Histone-Lysine N-Methyltransferase/metabolism; Methylation; Molecular Sequence Data; Nuclear Proteins/metabolism; RNA Interference; Receptor Protein-Tyrosine Kinases/metabolism; Signal Transduction; Transcription, Genetic; ras GTPase-Activating Proteins/metabolism; ras Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:G5EGI1

enables

GO:0042800: histone methyltransferase activity (H3-K4 specific)

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:G5EGI1

involved_in

GO:0051568: histone H3-K4 methylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:G5EGI1

involved_in

GO:0040028: regulation of vulval development

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00001515

P

Seeded From UniProt

complete


See also

References

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