Abstract
The SynMuv genes appear to be involved in providing a signal that inhibits vulval precursor cells from adopting vulval fates in Caenorhabditis elegans. One group of SynMuv genes, termed class B, includes genes encoding proteins related to the tumor suppressor Rb and RbAp48, a protein that binds Rb. Here, we provide genetic evidence that lin-13 behaves as a class B SynMuv gene. We show that null alleles of lin-13 are temperature sensitive and maternally rescued, resulting in phenotypes ranging in severity from L2 arrest (when both maternal and zygotic activities are removed at 25 degrees ), to sterile Multivulva (when only zygotic activity is removed at 25 degrees ), to sterile non-Multivulva (when both maternal and zygotic activities are removed at 15 degrees ), to wild-type/class B SynMuv (when only zygotic activity is removed at 15 degrees ). We also show that LIN-13 is a nuclear protein that contains multiple zinc fingers and a motif, LXCXE, that has been implicated in Rb binding. These results together suggest a role for LIN-13 in Rb-mediated repression of vulval fates.
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- Austin J., Kimble J. glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell. 1987 Nov 20;51(4):589–599. doi: 10.1016/0092-8674(87)90128-0. [DOI] [PubMed] [Google Scholar]
- Barstead R. J., Waterston R. H. The basal component of the nematode dense-body is vinculin. J Biol Chem. 1989 Jun 15;264(17):10177–10185. [PubMed] [Google Scholar]
- Beitel G. J., Clark S. G., Horvitz H. R. Caenorhabditis elegans ras gene let-60 acts as a switch in the pathway of vulval induction. Nature. 1990 Dec 6;348(6301):503–509. doi: 10.1038/348503a0. [DOI] [PubMed] [Google Scholar]
- Berg J. M. Zinc fingers and other metal-binding domains. Elements for interactions between macromolecules. J Biol Chem. 1990 Apr 25;265(12):6513–6516. [PubMed] [Google Scholar]
- Bettinger J. C., Lee K., Rougvie A. E. Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development. Development. 1996 Aug;122(8):2517–2527. doi: 10.1242/dev.122.8.2517. [DOI] [PubMed] [Google Scholar]
- Brehm A., Miska E. A., McCance D. J., Reid J. L., Bannister A. J., Kouzarides T. Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature. 1998 Feb 5;391(6667):597–601. doi: 10.1038/35404. [DOI] [PubMed] [Google Scholar]
- Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buyse I. M., Shao G., Huang S. The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4467–4471. doi: 10.1073/pnas.92.10.4467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- C. elegans Sequencing Consortium Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012–2018. doi: 10.1126/science.282.5396.2012. [DOI] [PubMed] [Google Scholar]
- Chalfie M., Tu Y., Euskirchen G., Ward W. W., Prasher D. C. Green fluorescent protein as a marker for gene expression. Science. 1994 Feb 11;263(5148):802–805. doi: 10.1126/science.8303295. [DOI] [PubMed] [Google Scholar]
- Clark S. G., Lu X., Horvitz H. R. The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins. Genetics. 1994 Aug;137(4):987–997. doi: 10.1093/genetics/137.4.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Costa M., Weir M., Coulson A., Sulston J., Kenyon C. Posterior pattern formation in C. elegans involves position-specific expression of a gene containing a homeobox. Cell. 1988 Dec 2;55(5):747–756. doi: 10.1016/0092-8674(88)90131-6. [DOI] [PubMed] [Google Scholar]
- Estevez M., Attisano L., Wrana J. L., Albert P. S., Massagué J., Riddle D. L. The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development. Nature. 1993 Oct 14;365(6447):644–649. doi: 10.1038/365644a0. [DOI] [PubMed] [Google Scholar]
- Fattaey A. R., Harlow E., Helin K. Independent regions of adenovirus E1A are required for binding to and dissociation of E2F-protein complexes. Mol Cell Biol. 1993 Dec;13(12):7267–7277. doi: 10.1128/mcb.13.12.7267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferguson E. L., Horvitz H. R. Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans. Genetics. 1985 May;110(1):17–72. doi: 10.1093/genetics/110.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferguson E. L., Horvitz H. R. The multivulva phenotype of certain Caenorhabditis elegans mutants results from defects in two functionally redundant pathways. Genetics. 1989 Sep;123(1):109–121. doi: 10.1093/genetics/123.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferguson E. L., Sternberg P. W., Horvitz H. R. A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans. Nature. 1987 Mar 19;326(6110):259–267. doi: 10.1038/326259a0. [DOI] [PubMed] [Google Scholar]
- Fire A., Harrison S. W., Dixon D. A modular set of lacZ fusion vectors for studying gene expression in Caenorhabditis elegans. Gene. 1990 Sep 14;93(2):189–198. doi: 10.1016/0378-1119(90)90224-f. [DOI] [PubMed] [Google Scholar]
- Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., Mello C. C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998 Feb 19;391(6669):806–811. doi: 10.1038/35888. [DOI] [PubMed] [Google Scholar]
- Freeman M., Klämbt C., Goodman C. S., Rubin G. M. The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye. Cell. 1992 Jun 12;69(6):963–975. doi: 10.1016/0092-8674(92)90615-j. [DOI] [PubMed] [Google Scholar]
- Fukushige T., Hendzel M. J., Bazett-Jones D. P., McGhee J. D. Direct visualization of the elt-2 gut-specific GATA factor binding to a target promoter inside the living Caenorhabditis elegans embryo. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11883–11888. doi: 10.1073/pnas.96.21.11883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ghiglione C., Carraway K. L., 3rd, Amundadottir L. T., Boswell R. E., Perrimon N., Duffy J. B. The transmembrane molecule kekkon 1 acts in a feedback loop to negatively regulate the activity of the Drosophila EGF receptor during oogenesis. Cell. 1999 Mar 19;96(6):847–856. doi: 10.1016/s0092-8674(00)80594-2. [DOI] [PubMed] [Google Scholar]
- Greenwald I. S., Horvitz H. R. unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype. Genetics. 1980 Sep;96(1):147–164. doi: 10.1093/genetics/96.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hedgecock E. M., Herman R. K. The ncl-1 gene and genetic mosaics of Caenorhabditis elegans. Genetics. 1995 Nov;141(3):989–1006. doi: 10.1093/genetics/141.3.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herman R. K., Hedgecock E. M. Limitation of the size of the vulval primordium of Caenorhabditis elegans by lin-15 expression in surrounding hypodermis. Nature. 1990 Nov 8;348(6297):169–171. doi: 10.1038/348169a0. [DOI] [PubMed] [Google Scholar]
- Hodgkin J., Papp A., Pulak R., Ambros V., Anderson P. A new kind of informational suppression in the nematode Caenorhabditis elegans. Genetics. 1989 Oct;123(2):301–313. doi: 10.1093/genetics/123.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horvitz H. R., Sulston J. E. Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans. Genetics. 1980 Oct;96(2):435–454. doi: 10.1093/genetics/96.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsieh J., Liu J., Kostas S. A., Chang C., Sternberg P. W., Fire A. The RING finger/B-box factor TAM-1 and a retinoblastoma-like protein LIN-35 modulate context-dependent gene silencing in Caenorhabditis elegans. Genes Dev. 1999 Nov 15;13(22):2958–2970. doi: 10.1101/gad.13.22.2958. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang L. S., Tzou P., Sternberg P. W. The lin-15 locus encodes two negative regulators of Caenorhabditis elegans vulval development. Mol Biol Cell. 1994 Apr;5(4):395–411. doi: 10.1091/mbc.5.4.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones R. E., Wegrzyn R. J., Patrick D. R., Balishin N. L., Vuocolo G. A., Riemen M. W., Defeo-Jones D., Garsky V. M., Heimbrook D. C., Oliff A. Identification of HPV-16 E7 peptides that are potent antagonists of E7 binding to the retinoblastoma suppressor protein. J Biol Chem. 1990 Aug 5;265(22):12782–12785. [PubMed] [Google Scholar]
- Klug A., Schwabe J. W. Protein motifs 5. Zinc fingers. FASEB J. 1995 May;9(8):597–604. [PubMed] [Google Scholar]
- Krause M., Hirsh D. A trans-spliced leader sequence on actin mRNA in C. elegans. Cell. 1987 Jun 19;49(6):753–761. doi: 10.1016/0092-8674(87)90613-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee J. O., Russo A. A., Pavletich N. P. Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7. Nature. 1998 Feb 26;391(6670):859–865. doi: 10.1038/36038. [DOI] [PubMed] [Google Scholar]
- Lu X., Horvitz H. R. lin-35 and lin-53, two genes that antagonize a C. elegans Ras pathway, encode proteins similar to Rb and its binding protein RbAp48. Cell. 1998 Dec 23;95(7):981–991. doi: 10.1016/s0092-8674(00)81722-5. [DOI] [PubMed] [Google Scholar]
- Luo R. X., Postigo A. A., Dean D. C. Rb interacts with histone deacetylase to repress transcription. Cell. 1998 Feb 20;92(4):463–473. doi: 10.1016/s0092-8674(00)80940-x. [DOI] [PubMed] [Google Scholar]
- Magnaghi-Jaulin L., Groisman R., Naguibneva I., Robin P., Lorain S., Le Villain J. P., Troalen F., Trouche D., Harel-Bellan A. Retinoblastoma protein represses transcription by recruiting a histone deacetylase. Nature. 1998 Feb 5;391(6667):601–605. doi: 10.1038/35410. [DOI] [PubMed] [Google Scholar]
- Mello C. C., Kramer J. M., Stinchcomb D., Ambros V. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 1991 Dec;10(12):3959–3970. doi: 10.1002/j.1460-2075.1991.tb04966.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller D. M., 3rd, Niemeyer C. J. Expression of the unc-4 homeoprotein in Caenorhabditis elegans motor neurons specifies presynaptic input. Development. 1995 Sep;121(9):2877–2886. doi: 10.1242/dev.121.9.2877. [DOI] [PubMed] [Google Scholar]
- Priess J. R., Hirsh D. I. Caenorhabditis elegans morphogenesis: the role of the cytoskeleton in elongation of the embryo. Dev Biol. 1986 Sep;117(1):156–173. doi: 10.1016/0012-1606(86)90358-1. [DOI] [PubMed] [Google Scholar]
- Pulak R., Anderson P. mRNA surveillance by the Caenorhabditis elegans smg genes. Genes Dev. 1993 Oct;7(10):1885–1897. doi: 10.1101/gad.7.10.1885. [DOI] [PubMed] [Google Scholar]
- Schultz J., Milpetz F., Bork P., Ponting C. P. SMART, a simple modular architecture research tool: identification of signaling domains. Proc Natl Acad Sci U S A. 1998 May 26;95(11):5857–5864. doi: 10.1073/pnas.95.11.5857. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seydoux G., Savage C., Greenwald I. Isolation and characterization of mutations causing abnormal eversion of the vulva in Caenorhabditis elegans. Dev Biol. 1993 Jun;157(2):423–436. doi: 10.1006/dbio.1993.1146. [DOI] [PubMed] [Google Scholar]
- Tevosian S. G., Shih H. H., Mendelson K. G., Sheppard K. A., Paulson K. E., Yee A. S. HBP1: a HMG box transcriptional repressor that is targeted by the retinoblastoma family. Genes Dev. 1997 Feb 1;11(3):383–396. doi: 10.1101/gad.11.3.383. [DOI] [PubMed] [Google Scholar]
- Thomas J. H., Horvitz H. R. The C. elegans gene lin-36 acts cell autonomously in the lin-35 Rb pathway. Development. 1999 Aug;126(15):3449–3459. doi: 10.1242/dev.126.15.3449. [DOI] [PubMed] [Google Scholar]
- Tong J. K., Hassig C. A., Schnitzler G. R., Kingston R. E., Schreiber S. L. Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex. Nature. 1998 Oct 29;395(6705):917–921. doi: 10.1038/27699. [DOI] [PubMed] [Google Scholar]
- Wilkinson H. A., Greenwald I. Spatial and temporal patterns of lin-12 expression during C. elegans hermaphrodite development. Genetics. 1995 Oct;141(2):513–526. doi: 10.1093/genetics/141.2.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Xue Y., Wong J., Moreno G. T., Young M. K., Côté J., Wang W. NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell. 1998 Dec;2(6):851–861. doi: 10.1016/s1097-2765(00)80299-3. [DOI] [PubMed] [Google Scholar]