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

Chromatin regulation and sumoylation in the inhibition of Ras-induced vulval development in Caenorhabditis elegans
Chromatin regulation and sumoylation in the inhibition of Ras-induced vulval development in Caenorhabditis elegans
In Caenorhaditis 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.
C. elegans, chromatin remodelling, ras signalling, RNAi, vulva
0261-4189
2613-2623
Poulin, Gino
0d913298-bea6-40db-987e-20ac92bc0875
Dong, Yan
902795e9-0f54-4051-9f89-21a7d2e63397
Fraser, Andrew G.
e3fccd51-7e18-493c-9b5a-a178bac481c3
Hopper, Neil A.
d2aed184-733b-47f6-8d74-fa1633ae6cf0
Ahringer, Julie
6a670bc7-c986-4257-92f2-ccd3c2996697
Poulin, Gino
0d913298-bea6-40db-987e-20ac92bc0875
Dong, Yan
902795e9-0f54-4051-9f89-21a7d2e63397
Fraser, Andrew G.
e3fccd51-7e18-493c-9b5a-a178bac481c3
Hopper, Neil A.
d2aed184-733b-47f6-8d74-fa1633ae6cf0
Ahringer, Julie
6a670bc7-c986-4257-92f2-ccd3c2996697

Poulin, Gino, Dong, Yan, Fraser, Andrew G., Hopper, Neil A. and Ahringer, Julie (2005) Chromatin regulation and sumoylation in the inhibition of Ras-induced vulval development in Caenorhabditis elegans. The EMBO Journal, 24 (14), 2613-2623. (doi:10.1038/sj.emboj.7600726).

Record type: Article

Abstract

In Caenorhaditis 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.

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More information

Submitted date: 11 August 2004
Published date: 20 July 2005
Keywords: C. elegans, chromatin remodelling, ras signalling, RNAi, vulva

Identifiers

Local EPrints ID: 32809
URI: https://eprints.soton.ac.uk/id/eprint/32809
ISSN: 0261-4189
PURE UUID: d71026d8-05c5-44de-bd16-34ffd1483660

Catalogue record

Date deposited: 12 May 2006
Last modified: 17 Jul 2017 15:54

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Contributors

Author: Gino Poulin
Author: Yan Dong
Author: Andrew G. Fraser
Author: Neil A. Hopper
Author: Julie Ahringer

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