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The C. elegans class A synthetic multivulva genes inhibit ectopic RAS-mediated vulval development by tightly restricting expression of lin-3 EGF

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dc.contributor.advisor H. Robert Horvitz. en_US
dc.contributor.author Saffer, Adam M en_US
dc.contributor.other Massachusetts Institute of Technology. Dept. of Biology. en_US
dc.date.accessioned 2011-05-09T14:01:56Z
dc.date.available 2011-05-09T14:01:56Z
dc.date.copyright 2011 en_US
dc.date.issued 2011 en_US
dc.identifier.uri http://hdl.handle.net/1721.1/62619
dc.description Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2011. en_US
dc.description This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. en_US
dc.description Cataloged from student-submitted PDF version of thesis. en_US
dc.description Includes bibliographical references (p. 236-259). en_US
dc.description.abstract The class A and B synthetic multivulva (synMuv) genes of C. elegans redundantly antagonize an EGF/Ras pathway to prevent ectopic vulval induction. The class B synMuv genes encode many proteins known to remodel chromatin and repress transcription. The class A synMuv genes likely also function in transcription, although their specific molecular functions are unknown. We have identified a class A synMuv mutation in the promoter of lin-3 EGF, revealing that lin-3 is the key biological target of the class A synMuv genes in vulval development. Using FISH with single mRNA molecule resolution, we found that class AB synMuv double mutants exhibit widespread ectopic lin-3 expression. Our results show that lin-3 EGF is normally expressed in the germline, and many class B synMuv genes have previously been implicated in inhibiting germline fates in somatic cells. We propose that the class A synMuv genes specifically repress ectopic lin-3 EGF expression through a site in the lin-3 promoter and the class B synMuv genes either directly or indirectly repress lin-3 as a consequence of their role in regulating the germline/soma distinction. The class A and B synMuv genes had previously been thought of as two parallel pathways, but we have found that each of those pathways is actually composed of multiple parallel pathways. While class AB synMuv double mutants have a strong Muv phenotype, most class AA synMuv double mutants exhibit a weak Muv phenotype, and most pairs of class B synMuv mutants can enhance each other in sensitized backgrounds, indicating that most genes within a class can function in parallel. We also found that some pairs of synMuv genes cannot act in parallel, indicating that they function together to repress ectopic lin-3 expression. We also report the molecular characterization of the class A synMuv gene lin-38 and the identification of mcd-1 as a class A synMuv gene. lin-38 and mcd-1 encode paralogous zinc-finger proteins. Unlike previously studied class A synMuv genes that function specifically in vulval development by repressing lin-3, both lin-38 and mcd-1 control multiple aspects of development by regulating target genes other than lin-3. en_US
dc.description.statementofresponsibility by Adam M. Saffer. en_US
dc.format.extent 259 p. en_US
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.rights.uri http://dspace.mit.edu/handle/1721.1/7582 en_US
dc.subject Biology. en_US
dc.title The C. elegans class A synthetic multivulva genes inhibit ectopic RAS-mediated vulval development by tightly restricting expression of lin-3 EGF en_US
dc.title.alternative Caenorhabditis elegans class A synthetic multivulva genes inhibit ectopic RAS-mediated vulval development by tightly restricting expression of lin-3 EGF en_US
dc.title.alternative C. elegans class A synMuv genes inhibit ectopic RAS-mediated vulval development by tightly restricting expression of lin-3 EGF en_US
dc.type Thesis en_US
dc.description.degree Ph.D. en_US
dc.contributor.department Massachusetts Institute of Technology. Dept. of Biology. en_US
dc.identifier.oclc 719387532 en_US


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