Characterization of the class A synthetic Multivulva genes, which act in C. elegans vulval development

The class A and B synthetic Multivulva (synMuv) genes function redundantly to inhibit Ras-mediated vulval development in C. elegans. The class B synMuv genes encode an Rb/DP/E2F repressor complex that likely silences genes required for vulval specification through chromatin modification and remodeling. Rb has been extensively characterized as a tumor suppressor gene in mammals. Of the four known class A synMuv genes, only the lin-15A locus was cloned previously and encodes a novel protein. To further our understanding both of the mechanism by which the synMuv A genes inhibit vulval induction and of the nature of their functional redundancy with Rb, we have cloned and characterized additional members of this pathway. We find that the class A synMuv gene lin-56 encodes a novel nuclear protein that shares an atypical CCCH motif with the class A synMuv protein LIN-15A. LIN-56 and LIN-15A depend on each other for wild-type protein levels. We propose that LIN-56 and LIN-15A normally associate in a functional complex required for vulval fate inhibition, and that complex formation is essential for the stability of both proteins. We find that a third class A synMuv gene, lin-8, is the defining member of a large and novel C. elegans gene family. The LIN-8 protein is also nuclear and interacts with the product of the class B synMuv gene lin-35, the C. elegans homologue of mammalian Rb. This is the first report of a direct molecular interaction between the class A and B synMuv pathways. Our data support a model in which the class A synMuv genes function in transcriptional regulation.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2003

Author dc:creator

• Davison, Ewa M., 1972-

Advisor dc:contributor.advisor

• H. Robert Horvitz.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/29366

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/29366