{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:55:52Z","timestamp":1791298552563,"version":"4.1.0"},"reference-count":46,"publisher":"The Company of Biologists","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,6,1]]},"abstract":"<jats:p>Twist is a transcription factor that is required for mesodermal cell fates in all animals studied to date. Mutations of this locus in humans have been identified as the cause of the craniofacial disorder Saethre-Chotzen syndrome. The Caenorhabditis elegans Twist homolog is required for the development of a subset of the mesoderm. A semidominant allele of the gene that codes for CeTwist, hlh-8, has defects that occur earlier in the mesodermal lineage than a previously studied null allele of the gene. The semidominant allele has a charge change (E29K) in the basic DNA-binding domain of CeTwist. Surprisingly, the mutant protein retains DNA-binding activity as both a homodimer and a heterodimer with its partner E\/Daughterless (CeE\/DA). However, the mutant protein blocks the activation of the promoter of a target gene. Therefore, the mutant CeTwist may cause cellular defects as a dominant negative protein by binding to target promoters as a homo- or heterodimer and then blocking transcription. Similar phenotypes as those caused by the E29K mutation were observed when amino acid substitutions in the DNA-binding domain that are associated with the human Saethre-Chotzen syndrome were engineered into the C. elegans protein. These data suggest that Saethre-Chotzen syndrome may be caused, in some cases, by dominant negative proteins, rather than by haploinsufficiency of the locus.<\/jats:p>","DOI":"10.1242\/dev.129.11.2761","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T04:52:03Z","timestamp":1619412723000},"page":"2761-2772","source":"Crossref","is-referenced-by-count":24,"title":["Characterization of a dominant negative<i>C. elegans<\/i>Twist mutant protein with implications for human Saethre-Chotzen syndrome"],"prefix":"10.1242","volume":"129","author":[{"given":"Ann K.","family":"Corsi","sequence":"first","affiliation":[{"name":"Department of Biology, The Catholic University of America, Washington, DC 20064, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Brodigan","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892-0510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik M.","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Utah, Salt Lake City, UT 84112-0840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Krause","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892-0510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042604171560000_BENGAL-ETAL-1994","doi-asserted-by":"crossref","unstructured":"Bengal, E., Flores, O., Rangarajan, P. N., Chen, A., Weintraub, H. and Verma, I. M. (1994). Positive control mutations in the MyoD basic region fail to show cooperative DNA binding and transcriptional activation in vitro. Proc. Natl. Acad. Sci. USA91, 6221-6225.","DOI":"10.1073\/pnas.91.13.6221"},{"key":"2021042604171560000_CASTANON-ETAL-2001","doi-asserted-by":"crossref","unstructured":"Castanon, I., von Stetina, S., Kass, J. and Baylies, M. K. (2001). Dimerization partners determine the activity of the Twist bHLH protein during Drosophila mesoderm development. Development128, 3145-3159.","DOI":"10.1242\/dev.128.16.3145"},{"key":"2021042604171560000_CHEN-AND-BEHRINGER-1995","doi-asserted-by":"crossref","unstructured":"Chen, Z. F. and Behringer, R. R. (1995). Twist is required in head mesenchyme for cranial neural tube morphogenesis. Genes Dev.9, 686-699.","DOI":"10.1101\/gad.9.6.686"},{"key":"2021042604171560000_COHEN-2000","unstructured":"Cohen, M. M., Jr (2000). Saethre-Chotzen syndrome. In Craniosynostosis: Diagnosis, Evaluation, and Management (ed. M. M. Cohen, Jr and R. E. MacLean), pp. 374-376. New York, NY: Oxford University Press."},{"key":"2021042604171560000_CORSI-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Corsi, A. K., Kostas, S. A., Fire, A. and Krause, M. (2000). Caenorhabditis elegans Twist plays an essential role in non-striated muscle development. Development127, 2041-2051.","DOI":"10.1242\/dev.127.10.2041"},{"key":"2021042604171560000_DONG-ETAL-2000","unstructured":"Dong, M. Q., Chase, D., Patikoglou, G. A. and Koelle, M. R. (2000). Multiple RGS proteins alter neural G protein signaling to allow C. elegans to rapidly change behavior when fed. Genes Dev.14, 2003-2014."},{"key":"2021042604171560000_EL-GHOUZZI-ETAL-2000","doi-asserted-by":"crossref","unstructured":"El Ghouzzi, V., Legeai-Mallet, L., Aresta, S., Benoist, C., Munnich, A., de Gunzburg, J. and Bonaventure, J. (2000). Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location. Hum. Mol. Genet.9, 813-819.","DOI":"10.1093\/hmg\/9.5.813"},{"key":"2021042604171560000_ELLENBERGER-ETAL-1994","doi-asserted-by":"crossref","unstructured":"Ellenberger, T., Fass, D., Arnaud, M. and Harrison, S. C. (1994). Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer. Genes Dev.8, 970-980.","DOI":"10.1101\/gad.8.8.970"},{"key":"2021042604171560000_GRIPP-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Gripp, K. W., Zackai, E. H. and Stolle, C. A. (2000). Mutations in the human TWIST gene. Hum. Mutat.15, 150-155.","DOI":"10.1002\/(SICI)1098-1004(200002)15:2<150::AID-HUMU3>3.0.CO;2-D"},{"key":"2021042604171560000_HARFE-AND-FIRE-1998","doi-asserted-by":"crossref","unstructured":"Harfe, B. D. and Fire, A. (1998). Muscle and nerve-specific regulation of a novel NK-2 class homeodomain factor in Caenorhabditis elegans. Development125, 421-429.","DOI":"10.1242\/dev.125.3.421"},{"key":"2021042604171560000_HARFE-ETAL-1998A","doi-asserted-by":"crossref","unstructured":"Harfe, B. D., Branda, C. S., Krause, M., Stern, M. J. and Fire, A. (1998a). MyoD and the specification of muscle and non-muscle fates during postembryonic development of the C. elegans mesoderm. Development125, 2479-2488.","DOI":"10.1242\/dev.125.13.2479"},{"key":"2021042604171560000_HARFE-ETAL-1998B","doi-asserted-by":"crossref","unstructured":"Harfe, B. D., Gomes, A. V., Kenyon, C., Liu, J., Krause, M. and Fire, A. (1998b). Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning. Genes Dev.12, 2623-2635.","DOI":"10.1101\/gad.12.16.2623"},{"key":"2021042604171560000_HEHR-AND-MUENKE-1999","doi-asserted-by":"crossref","unstructured":"Hehr, U. and Muenke, M. (1999). Craniosynostosis syndromes: from genes to premature fusion of skull bones. Mol. Genet. Metab.68, 139-151.","DOI":"10.1006\/mgme.1999.2915"},{"key":"2021042604171560000_HOPWOOD-ETAL-1989","doi-asserted-by":"crossref","unstructured":"Hopwood, N. D., Pluck, A. and Gurdon, J. B. (1989). A Xenopus mRNA related to Drosophila twist is expressed in response to induction in the mesoderm and the neural crest. Cell59, 893-903.","DOI":"10.1016\/0092-8674(89)90612-0"},{"key":"2021042604171560000_HOWARD-ETAL-1997","doi-asserted-by":"crossref","unstructured":"Howard, T. D., Paznekas, W. A., Green, E. D., Chiang, L. C., Ma, N., Ortiz de Luna, R. I., Garcia Delgado, C., Gonzalez-Ramos, M., Kline, A. D. and Jabs, E. W. (1997). Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. Nat. Genet.15, 36-41.","DOI":"10.1038\/ng0197-36"},{"key":"2021042604171560000_HUANG-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Huang, J., Weintraub, H. and Kedes, L. (1998). Intramolecular regulation of MyoD activation domain conformation and function. Mol. Cell Biol.18, 5478-5484.","DOI":"10.1128\/MCB.18.9.5478"},{"key":"2021042604171560000_JOHNSON-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Johnson, D., Horsley, S. W., Moloney, D. M., Oldridge, M., Twigg, S. R., Walsh, S., Barrow, M., Njolstad, P. R., Kunz, J., Ashworth, G. J. et al. (1998). A comprehensive screen for TWIST mutations in patients with craniosynostosis identifies a new microdeletion syndrome of chromosome band 7p21.1. Am. J. Hum. Genet.63, 1282-1293.","DOI":"10.1086\/302122"},{"key":"2021042604171560000_KRAUSE-ETAL-1990","doi-asserted-by":"crossref","unstructured":"Krause, M., Fire, A., Harrison, S. W., Priess, J. and Weintraub, H. (1990). CeMyoD accumulation defines the body wall muscle cell fate during C. elegans embryogenesis. Cell63, 907-919.","DOI":"10.1016\/0092-8674(90)90494-Y"},{"key":"2021042604171560000_KRAUSE-ETAL-1997","unstructured":"Krause, M., Park, M., Zhang, J. M., Yuan, J., Harfe, B., Xu, S. Q., Greenwald, I., Cole, M., Paterson, B. and Fire, A. (1997). A C. elegans E\/Daughterless bHLH protein marks neuronal but not striated muscle development. Development124, 2179-2189."},{"key":"2021042604171560000_LAJEUNIE-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Lajeunie, E., Catala, M. and Renier, D. (1999). Craniosynostosis: from a clinical description to an understanding of bone formation of the skull. Childs Nerv. Syst.15, 676-680.","DOI":"10.1007\/s003810050457"},{"key":"2021042604171560000_LASSAR-ETAL-1991","doi-asserted-by":"crossref","unstructured":"Lassar, A. B., Davis, R. L., Wright, W. E., Kadesch, T., Murre, C., Voronova, A., Baltimore, D. and Weintraub, H. (1991). Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12\/E47-like proteins in vivo. Cell66, 305-315.","DOI":"10.1016\/0092-8674(91)90620-E"},{"key":"2021042604171560000_LEDENT-AND-VERVOORT-2001","doi-asserted-by":"crossref","unstructured":"Ledent, V. and Vervoort, M. (2001). The basic helix-loop-helix protein family: comparative genomics and phylogenetic analysis. Genome Res.11, 754-770.","DOI":"10.1101\/gr.177001"},{"key":"2021042604171560000_MA-ETAL-1994","doi-asserted-by":"crossref","unstructured":"Ma, P. C., Rould, M. A., Weintraub, H. and Pabo, C. O. (1994). Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation. Cell77, 451-459.","DOI":"10.1016\/0092-8674(94)90159-7"},{"key":"2021042604171560000_MASSARI-AND-MURRE-2000","doi-asserted-by":"crossref","unstructured":"Massari, M. E. and Murre, C. (2000). Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol. Cell. Biol.20, 429-440.","DOI":"10.1128\/MCB.20.2.429-440.2000"},{"key":"2021042604171560000_MELLO-AND-FIRE-1995","unstructured":"Mello, C. C. and Fire, A. (1995). DNA transformation. In Caenorhabditis elegans: Modern Biological Analysis of an Organism (ed. H. F. Epstein and D. C. Shakes), pp. 452-482. San Diego, CA: Academic Press."},{"key":"2021042604171560000_MELLO-ETAL-1991","unstructured":"Mello, C. C., Kramer, J. M., Stinchcomb, D. and Ambros, V. (1991). Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J.10, 3959-3970."},{"key":"2021042604171560000_MELLO-ETAL-1994","doi-asserted-by":"crossref","unstructured":"Mello, C. C., Draper, B. W. and Priess, J. R. (1994). The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral polarity in the early C. elegans embryo. Cell77, 95-106.","DOI":"10.1016\/0092-8674(94)90238-0"},{"key":"2021042604171560000_MOERMAN-AND-FIRE-1997","unstructured":"Moerman, D. G. and Fire, A. (1997). Muscle: Structure, function, and development. In Caenorhabditis elegans II (ed. D. L. Riddle, T. Blumenthal, B. J. Meyer and J. R. Priess), pp. 417-470. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press."},{"key":"2021042604171560000_MURRE-ETAL-1989","doi-asserted-by":"crossref","unstructured":"Murre, C., McCaw, P. S., Vaessin, H., Caudy, M., Jan, L. Y., Jan, Y. N., Cabrera, C. V., Buskin, J. N., Hauschka, S. D., Lassar, A. B. et al. (1989). Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell58, 537-544.","DOI":"10.1016\/0092-8674(89)90434-0"},{"key":"2021042604171560000_NUUMLSSLEIN-VOLHARD-ETAL-1984","doi-asserted-by":"crossref","unstructured":"Nu\u0308sslein-Volhard, C., Wieschaus, E., and Kluding, H. (1984). Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster. Roux\u2019s Arch. Dev. Biol.193, 267-282.","DOI":"10.1007\/BF00848156"},{"key":"2021042604171560000_PAZNEKAS-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Paznekas, W. A., Cunningham, M. L., Howard, T. D., Korf, B. R., Lipson, M. H., Grix, A. W., Feingold, M., Goldberg, R., Borochowitz, Z., Aleck, K. et al. (1998). Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations. Am. J. Hum. Genet.62, 1370-1380.","DOI":"10.1086\/301855"},{"key":"2021042604171560000_REARDON-AND-WINTER-1994","doi-asserted-by":"crossref","unstructured":"Reardon, W. and Winter, R. M. (1994). Saethre-Chotzen syndrome. J. Med. Genet.31, 393-396.","DOI":"10.1136\/jmg.31.5.393"},{"key":"2021042604171560000_REARDON-AND-WINTER-1995","doi-asserted-by":"crossref","unstructured":"Reardon, W. and Winter, R. M. (1995). The molecular pathology of syndromic craniosynostosis. Mol. Med. Today1, 432-437.","DOI":"10.1016\/S1357-4310(95)90837-4"},{"key":"2021042604171560000_ROSE-ETAL-1997","doi-asserted-by":"crossref","unstructured":"Rose, C. S., Patel, P., Reardon, W., Malcolm, S. and Winter, R. M. (1997). The TWIST gene, although not disrupted in Saethre-Chotzen patients with apparently balanced translocations of 7p21, is mutated in familial and sporadic cases. Hum. Mol. Genet.6, 1369-1373.","DOI":"10.1093\/hmg\/6.8.1369"},{"key":"2021042604171560000_RUVKUN-AND-HOBERT-1998","doi-asserted-by":"crossref","unstructured":"Ruvkun, G. and Hobert, O. (1998). The taxonomy of developmental control in Caenorhabditis elegans. Science282, 2033-2041.","DOI":"10.1126\/science.282.5396.2033"},{"key":"2021042604171560000_SIEBER-AND-ALLEMANN-1998","unstructured":"Sieber, M. and Allemann, R. K. (1998). Arginine (348) is a major determinant of the DNA binding specificity of transcription factor E12. Biol. Chem.379, 731-735."},{"key":"2021042604171560000_SIMPSON-1983","doi-asserted-by":"crossref","unstructured":"Simpson, P. (1983). Maternal-zygotic gene interactions during formation of the dorsoventral pattern in Drosophila embryos. Genetics105, 615-632.","DOI":"10.1093\/genetics\/105.3.615"},{"key":"2021042604171560000_SPICER-ETAL-1996","doi-asserted-by":"crossref","unstructured":"Spicer, D. B., Rhee, J., Cheung, W. L. and Lassar, A. B. (1996). Inhibition of myogenic bHLH and MEF2 transcription factors by the bHLH protein Twist. Science272, 1476-1480.","DOI":"10.1126\/science.272.5267.1476"},{"key":"2021042604171560000_SULSTON-AND-HORVITZ-1977","doi-asserted-by":"crossref","unstructured":"Sulston, J. E. and Horvitz, H. R. (1977). Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev. Biol.56, 110-156.","DOI":"10.1016\/0012-1606(77)90158-0"},{"key":"2021042604171560000_THISSE-ETAL-1988","doi-asserted-by":"crossref","unstructured":"Thisse, B., Stoetzel, C., Gorostiza-Thisse, C. and Perrin-Schmitt, F. (1988). Sequence of the twist gene and nuclear localization of its protein in endomesodermal cells of early Drosophila embryos. EMBO J.7, 2175-2183.","DOI":"10.1002\/j.1460-2075.1988.tb03056.x"},{"key":"2021042604171560000_VITOLA-ETAL-1996","doi-asserted-by":"crossref","unstructured":"Vitola, S. J., Wang, A. and Sun, X. H. (1996). Substitution of basic amino acids in the basic region stabilizes DNA binding by E12 homodimers. Nucleic Acids Res.24, 1921-1927.","DOI":"10.1093\/nar\/24.10.1921"},{"key":"2021042604171560000_WANG-ETAL-1997","doi-asserted-by":"crossref","unstructured":"Wang, S. M., Coljee, V. W., Pignolo, R. J., Rotenberg, M. O., Cristofalo, V. J. and Sierra, F. (1997). Cloning of the human twist gene: its expression is retained in adult mesodermally-derived tissues. Gene187, 83-92.","DOI":"10.1016\/S0378-1119(96)00727-5"},{"key":"2021042604171560000_WATERSTON-1988","unstructured":"Waterston, R. H. (1988). Muscle. In The Nematode Caenorhabditis elegans (ed. W. B. Wood), pp. 281-335. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press."},{"key":"2021042604171560000_WILKIE-1997","doi-asserted-by":"crossref","unstructured":"Wilkie, A. O. (1997). Craniosynostosis: genes and mechanisms. Hum. Mol. Genet.6, 1647-1656.","DOI":"10.1093\/hmg\/6.10.1647"},{"key":"2021042604171560000_WILLIAMS-1995","doi-asserted-by":"crossref","unstructured":"Williams, B. D. (1995). Genetic mapping with polymorphic sequence-tagged sites. In Caenorhabditis elegans: Modern Biological Analysis of an Organism (ed. H. F. Epstein and D. C. Shakes), pp. 81-96. New York: Academic Press.","DOI":"10.1016\/S0091-679X(08)61384-9"},{"key":"2021042604171560000_WOLF-ETAL-1991","doi-asserted-by":"crossref","unstructured":"Wolf, C., Thisse, C., Stoetzel, C., Thisse, B., Gerlinger, P. and Perrin-Schmitt, F. (1991). The M-twist gene of Mus is expressed in subsets of mesodermal cells and is closely related to the Xenopus X-twi and the Drosophila twist genes. Dev. Biol.143, 363-373.","DOI":"10.1016\/0012-1606(91)90086-I"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/129\/11\/2761\/1139298\/2761.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/129\/11\/2761\/1139298\/2761.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T11:58:52Z","timestamp":1671969532000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/129\/11\/2761\/41685\/Characterization-of-a-dominant-negative-C-elegans"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,6,1]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2002,6,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.129.11.2761","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2002,6,1]]}}}