Davison, Ewa M. and Saffer, Adam M. and Huang, Linda S. and DeModena, John and Sternberg, Paul W. and Horvitz, H. Robert (2011) The LIN-15A and LIN-56 Transcriptional Regulators Interact to Negatively Regulate EGF/Ras Signaling in Caenorhabditis elegans Vulval Cell-Fate Determination. Genetics, 187 (3). pp. 803-815. ISSN 0016-6731. PMCID PMC3063674. https://resolver.caltech.edu/CaltechAUTHORS:20110401-135236894
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Abstract
The restricted expression of epidermal growth factor (EGF) family ligands is important for proper development and for preventing cancerous growth in mammals. In Caenorhabditis elegans, the class A and B synthetic multivulva (synMuv) genes redundantly repress expression of lin-3 EGF to negatively regulate Ras-mediated vulval development. The class B synMuv genes encode proteins homologous to components of the NuRD and Myb-MuvB/dREAM transcriptional repressor complexes, indicating that they likely silence lin-3 EGF through chromatin remodeling. The two class A synMuv genes cloned thus far, lin-8 and lin-15A, both encode novel proteins. The LIN-8 protein is nuclear. We have characterized the class A synMuv gene lin-56 and found it to encode a novel protein that shares a THAP-like C_2CH motif with LIN-15A. Both the LIN-56 and LIN-15A proteins localize to nuclei. Wild-type levels of LIN-56 require LIN-15A, and wild-type levels and/or localization of LIN-15A requires LIN-56. Furthermore, LIN-56 and LIN-15A interact in the yeast two-hybrid system. We propose that LIN-56 and LIN-15A associate in a nuclear complex that inhibits vulval specification by repressing lin-3 EGF expression.
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| Additional Information: | © 2011 Genetics Society of America. Manuscript received October 21, 2010. Accepted for publication December 21, 2010. Originally published as Genetics Advance Online Publication on December 31, 2010. Communicating editor: D. I. Greenstein. We thank Erik Andersen, Craig Ceol, Alison Frand, and Niels Ringstad for editorial comments; Melissa Harrison for help with yeast two-hybrid analysis; Erik Andersen for construction of lin-15A and lin-56 Gateway entry clones; Beth Castor for help with DNA sequence determination; Na An for strain management; Yuji Kohara for EST cDNA clones; Alan Coulson and the C. elegans Sequencing Consortium for cosmid clones and sequences; and Steve Bell for use of the ABI PRISM 7000 Sequence Detection System. The deficiency strains were provided by Theresa Stiernagle of the Caenorhabditis Genetics Center, which is supported by the National Institutes of Health (NIH) National Center for Research Resources. This work was supported by NIH grant GM24663 (to H.R.H.) and a Howard Hughes Medical Institute predoctoral fellowship (to E.M.D.). L.S.H. was supported by a March of Dimes Birth Defects Foundation grant (to P.W.S.). H.R.H. and P.W.S. are Investigators of the Howard Hughes Medical Institute. | |||||||||
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| Issue or Number: | 3 | |||||||||
| PubMed Central ID: | PMC3063674 | |||||||||
| Record Number: | CaltechAUTHORS:20110401-135236894 | |||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20110401-135236894 | |||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
| ID Code: | 23208 | |||||||||
| Collection: | CaltechAUTHORS | |||||||||
| Deposited By: | Tony Diaz | |||||||||
| Deposited On: | 29 Jun 2011 23:07 | |||||||||
| Last Modified: | 03 Oct 2019 02:44 |
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