Rb pathway and chromatin remodeling genes that antagonize let-60 Ras signaling during C. elegans vulval development

The synthetic multivulva (synMuv) class A and class B genes act redundantly to regulate Ras-mediated vulval cell fate specification in the nematode Caenorhabditis elegans. The class B synMuv gene lin-35 encodes a protein similar to the mammalian pRb tumor suppressor protein. The LIN-35 Rb protein is proposed to act with HDA-1, a histone deacetylase homolog with class B synMuv activity, to remodel chromatin and repress transcription of genes that promote vulval development. To further understand how lin-35 Rb and hda-1 regulate vulval cell fate specification, we identified and characterized additional class B synMuv genes. We found that two of these genes, dpl-1 and efl-1, encode homologs of DP and E2F DNA-binding transcription factors, respectively. Loss-of-function mutations in dpl-1 and efl- 1 cause the same synMuv phenotype as do lin-35 Rb loss-of-function mutations, and the DPL-1 and EFL-1 proteins interact with each other and with LIN-35 Rb in vitro. These data suggest that, in the context of vulval development, DPL-1 and EFL-1 recruit LIN-35 Rb, HDA-1 and other synMuv proteins to DNA to repress transcription. We found that the class B synMuv genes lin-52 and lin-54 encode novel, conserved proteins. The cysteine-rich LIN-54 protein is localized to nuclei and interacts with the class B synMuv protein LIN-36 in vitro. Homologs of lin-52 and lin-54 are candidate Rb pathway genes in other organisms. We performed a genetic screen for synMuv mutations and identified seven new synMuv genes.

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

• Ceol, Craig J. (Craig Joseph), 1971-

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/1721.1/32260

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/32260