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

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dc.contributor.advisor H. Robert Horvitz. en_US Ceol, Craig J. (Craig Joseph), 1971- en_US
dc.contributor.other Massachusetts Institute of Technology. Dept. of Biology. en_US 2006-03-29T18:28:38Z 2006-03-29T18:28:38Z 2002 en_US 2003 en_US
dc.description Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, February 2003. en_US
dc.description Includes bibliographical references. en_US
dc.description.abstract 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. en_US
dc.description.abstract (cont.) We found that one of these genes, mep-1, encodes a zinc-finger protein. Mutations affecting another gene identified in this screen, trr-1, synergize with either class A or class B mutations, thus defining a new class of synMuv gene. trr-1 encodes a protein similar to the mammalian TRRAP transcriptional adaptor protein. We identified hat-1 and epc-1, which encode homologs of TRRAP-associated histone acetyltransferase and Enhancer of Polycomb-like proteins, respectively, as additional members of this new class of synMuv genes. The synMuv activities of both hat-1 and hda-1 suggest that a combination of histone acetyltransferase and histone deacetylase activities are required to properly specify vulval cell fates. en_US
dc.description.statementofresponsibility by Craig J. Ceol. en_US
dc.format.extent 2 v. (309 leaves) en_US
dc.format.extent 11943696 bytes
dc.format.extent 11939300 bytes
dc.format.mimetype application/pdf
dc.format.mimetype application/pdf
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
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. en_US
dc.subject Biology. en_US
dc.title Rb pathway and chromatin remodeling genes that antagonize let-60 Ras signaling during C. elegans vulval development en_US
dc.title.alternative Retinoblastoma susceptibility gene pathway and chromatin remodeling genes that antagonize let-60 Ras signaling during C. elegans vulval development en_US
dc.type Thesis en_US Ph.D. en_US
dc.contributor.department Massachusetts Institute of Technology. Dept. of Biology. en_US
dc.identifier.oclc 56024567 en_US

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