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Chromatin regulation and sumoylation in the inhibition of Ras‐induced vulval development in Caenorhabditis elegans

Gino Poulin, Yan Dong, Andrew G Fraser, Neil A Hopper, Julie Ahringer

Author Affiliations

  1. Gino Poulin1,2,
  2. Yan Dong1,2,
  3. Andrew G Fraser1,,
  4. Neil A Hopper3 and
  5. Julie Ahringer*,1,2
  1. 1 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK
  2. 2 Department of Genetics, University of Cambridge, Cambridge, UK
  3. 3 School of Biological Sciences, University of Southampton, Southampton, UK
  1. *Corresponding author. Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK. Tel.: +44 1223 334088; Fax: +44 1223 334089; E‐mail: jaa{at}mole.bio.cam.ac.uk
  • Present address: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK

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Abstract

In Caenorhabditis elegans, numerous ‘synMuv’ (synthetic multivulval) genes encode for chromatin‐associated proteins involved in transcriptional repression, including an orthologue of Rb and components of the NuRD histone deacetylase complex. These genes antagonize Ras signalling to prevent erroneous adoption of vulval fate. To identify new components of this mechanism, we performed a genome‐wide RNA interference (RNAi) screen. After RNAi of 16 757 genes, we found nine new synMuv genes. Based on predicted functions and genetic epistasis experiments, we propose that at least four post‐translational modifications converge to inhibit Ras‐stimulated vulval development: sumoylation, histone tail deacetylation, methylation, and acetylation. In addition, we demonstrate a novel role for sumoylation in inhibiting LIN‐12/Notch signalling in the vulva. We further show that many of the synMuv genes are involved in gene regulation outside the vulva, negatively regulating the expression of the Delta homologue lag‐2. As most of the genes identified in this screen are conserved in humans, we suggest that similar interactions may be relevant in mammals for control of Ras and Notch signalling, crosstalk between these pathways, and cell proliferation.

  • Received August 11, 2004.
  • Accepted June 3, 2005.
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