Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Sign up for alerts
  • About us
    • About Development
    • About the Node
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contacts
    • Subscriptions
    • Advertising
    • Feedback
    • For library administrators
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in
  • Log out

Search

  • Advanced search
Development
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Development

  • Log in
Advanced search

RSS  Twitter  Facebook  YouTube 

  • Home
  • Articles
    • Accepted manuscripts
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Sign up for alerts
  • About us
    • About Development
    • About the Node
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contacts
    • Subscriptions
    • Advertising
    • Feedback
    • For library administrators
JOURNAL ARTICLES
lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H)
S. Christensen, V. Kodoyianni, M. Bosenberg, L. Friedman, J. Kimble
Development 1996 122: 1373-1383;
S. Christensen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
V. Kodoyianni
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Bosenberg
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. Friedman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Kimble
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & metrics
  • PDF
Loading

Summary

The homologous receptors LIN-12 and GLP-1 mediate diverse cell-signaling events during development of the nematode Caenorhabditis elegans. These two receptors appear to be functionally interchangeable and have sequence similarity to Drosophila Notch. Here we focus on a molecular analysis of the lag-1 gene (lin-12 -and glp-1), which plays a central role in LIN-12 and GLP-1-mediated signal transduction. We find that the predicted LAG-1 protein is homologous to two DNA-binding proteins: human C Promoter Binding Factor (CBF1) and Drosophila Suppressor of Hairless (Su(H)). Furthermore, we show that LAG-1 binds specifically to the DNA sequence RTGGGAA, previously identified as a CBF-1/Su(H)-binding site. Finally, we report that the 5′ flanking regions and first introns of the lin-12, glp-1 and lag-1 genes are enriched for potential LAG-1-binding sites. We propose that LAG-1 is a transcriptional regulator that serves as a primary link between the LIN-12 and GLP-1 receptors and downstream target genes in C. elegans. In addition, we propose that LAG-1 may be a key component of a positive feedback loop that amplifies activity of the LIN-12/GLP-1 pathway.

Reference

    1. Amakawa R.,
    2. Jing W.,
    3. Ozawa K.,
    4. Matsunami N.,
    5. Hamaguchi Y.,
    6. Matsuda F.,
    7. Kawaichi M.,
    8. Honjo T.
    (1993) Human Jrecombination signal binding protein gene (IGKJRB): comparison with its mouse homologue. Genomics 17, 306–315
    OpenUrlCrossRefPubMedWeb of Science
    1. Artavanis-Tsakonas S.,
    2. Matsuno K.,
    3. Fortini M. E.
    (1995) Notch signaling. Science 268, 225–232
    OpenUrlAbstract/FREE Full Text
    1. Bailey A. M.,
    2. Posakony J. W.
    (1995) Supppressor of Hairless directly activates transcripton of Enhancer of split Complex genes in response to Notch receptor activity. Genes Dev 9, 2609–2622
    OpenUrlAbstract/FREE Full Text
    1. Brou C.,
    2. Logeat F.,
    3. Lecourtois M.,
    4. Vanderkerckhove J.,
    5. Kourilsky P.,
    6. Schweisguth F.,
    7. Israel A.
    (1994) Inhibition of the DNA-binding activity of Drosophila Suppressor of Hairless and of its human homolog, KBF2/RBP-J, by direct protein-protein interaction with Drosophila Hairless. Genes Dev 8, 2491–2503
    OpenUrlAbstract/FREE Full Text
    1. Chelsky D.,
    2. Ralph R.,
    3. Jonak G.
    (1989) Sequence requirements for synthetic peptide-mediated translocation to the nucleus. Mol. Cell Biol 9, 2487–2492
    OpenUrlAbstract/FREE Full Text
    1. Clark-Lewis I.,
    2. Sanghera J. S.,
    3. Pelech S. L.
    (1991) Definition of a consensus sequence for peptide substrate recognition by p44mpk, the meiosis activated myelin basic protein kinase. J.Biol. Chem 266, 15180–15184
    OpenUrlAbstract/FREE Full Text
    1. Devereux J.,
    2. Haeberli P.,
    3. Smithies O.
    (1984) A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Research 12, 387–395
    1. Dou S.,
    2. Zeng X.,
    3. Cortes P.,
    4. Erdjument-Bromage H.,
    5. Tempst P.,
    6. Honjo T.,
    7. Vales L. D.
    (1994) The recombination signal sequence-binding protein RBP-2N functions as a transciptional repressor. Mol. Cell Biol 14, 3310–3319
    OpenUrlAbstract/FREE Full Text
    1. Fitzgerald K.,
    2. Wilkinson H.,
    3. Greenwald I.
    (1993) glp-1 can substitute for lin-12 in specifying cell fate decisions in Caenorhabditis elegans. Development 119, 1019–1027
    OpenUrlAbstract
    1. Fitzgerald K.,
    2. Greenwald I.
    (1995) Interchangeablility of Caenorhabditis elegans DSL proteins and intrinsic signalling activity of their extracellular domains in vivo. Development 121, 4275–4282
    OpenUrlAbstract
    1. Fortini M. E.,
    2. Artavanis-Tsakonas S.
    (1994) The Suppressor of Hairless protein participates in Notch receptor signaling. Cell 79, 273–282
    OpenUrlCrossRefPubMedWeb of Science
    1. Frohman M. A.,
    2. Dush M. K.,
    3. Martin G. R.
    (1988) Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc. Nat. Acad. Sci. USA 85, 8998–9002
    OpenUrlAbstract/FREE Full Text
    1. Furukawa T.,
    2. Kawaichi M.,
    3. Matsunami N.,
    4. Ryo H.,
    5. Nishida Y.,
    6. Honjo T.
    (1991) The Drosophila RBP-Jgene encodes the binding protein for the immunoglobulin J recombination signal sequence. J. Biol. Chem 266, 23334–23340
    OpenUrlAbstract/FREE Full Text
    1. Gao D.,
    2. Kimble J.
    (1995) APX-1 can substitute for its homolog LAG-2 to direct cell interactions throughout Caenorhabditis elegans development. Proc. Nat. Acad. Sci. USA 92, 9839–9842
    OpenUrlAbstract/FREE Full Text
    1. Greenwald I.
    (1985) lin-12, a nematode homeotic gene, is homologous to a set of mammalian proteins that includes epidermal growth factor. Cell 43, 583–590
    OpenUrlCrossRefPubMedWeb of Science
    1. Grossman S. R.,
    2. Johannsen E.,
    3. Tong X.,
    4. Yalamanchili R.,
    5. Kieff E.
    (1994) The Epstein-Barr virus nuclear antigen 2 transactivator is directed to response elements by the Jrecombination signal binding protein. Proc. Natl. Acad. Sci. USA 91, 7568–7572
    OpenUrlAbstract/FREE Full Text
    1. Heitzler P.,
    2. Simpson P.
    (1991) The choice of cell fate in the epidermis of Drosophila. Cell 64, 1083–1092
    OpenUrlCrossRefPubMedWeb of Science
    1. Henderson S. T.,
    2. Gao D.,
    3. Lambie E. J.,
    4. Kimble J.
    (1994) lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans. Development 120, 2913–2924
    OpenUrlAbstract
    1. Henkel T.,
    2. Ling P. D.,
    3. Hayward S. D.,
    4. Peterson M. G.
    (1994) Mediation of Epstein-Barr Virus EBNA2 transactivation by recombination signal-binding protein J. Science 265, 92–95
    OpenUrlAbstract/FREE Full Text
    1. Henrique D.,
    2. Adam J.,
    3. Myat A.,
    4. Chitnis A.,
    5. Lewis J.,
    6. Ish-Horowicz D.
    (1995) Expression of a Delta homologue in prospective neurons in the chick. Nature 375, 787–790
    OpenUrlCrossRefPubMedWeb of Science
    1. Hodgkin J.,
    2. Papp A.,
    3. Pulak R.,
    4. Ambros V.,
    5. Anderson P.
    (1989) A new kind of informational suppression in the nematode Caenorhabditis elegans. Genetics 123, 301–313
    OpenUrlAbstract/FREE Full Text
    1. Horvitz H. R.,
    2. Brenner S.,
    3. Hodgkin J.,
    4. Herman R. K.
    (1979) A uniform genetic nomenclature for the nematode Caenorhabditis elegans. Mol. Gen. Genet 175, 129–33
    OpenUrlCrossRefPubMedWeb of Science
    1. Hsieh J. J.-D.,
    2. Hayward S. D.
    (1995) Masking of the CBF1/RBP Jtranscriptional repression domain by Epstein-Barr virus EBNA2. Science 268, 560–563
    OpenUrlAbstract/FREE Full Text
    1. Hutter H.,
    2. Schnabel R.
    (1994) glp-1 and inductions establishing embryonic axes in C. elegans. Development 120, 2051–2064
    OpenUrlAbstract
    1. Jarriault S.,
    2. Brou C.,
    3. Logeat F.,
    4. Schroeter E. H.,
    5. Kopan R.,
    6. Israël A.
    (1995) Signaling downstream of activated mammalian Notch. Nature 377, 355–358
    OpenUrlCrossRefPubMedWeb of Science
    1. Kodoyianni V.,
    2. Maine E. M.,
    3. Kimble J.
    (1992) Molecular basis of loss-of-function mutations in the glp-1 gene of Caenorhabditis elegans. Mol. Biol. Cell 3, 1199–1213
    OpenUrlAbstract/FREE Full Text
    1. Lambie E. J.,
    2. Kimble J.
    (1991) Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions. Development 112, 231–240
    OpenUrlAbstract
    1. Lecourtois M.,
    2. Schweisguth F.
    (1995) The neurogenic Suppressor of Hairless DNA-binding protein mediates the transcriptional activation of the Enhancer of split Complex genes triggered by Notch signaling. Genes Dev 9, 2598–2608
    OpenUrlAbstract/FREE Full Text
    1. Mango S. E.,
    2. Maine E. M.,
    3. Kimble J.
    (1991) Carboxy-terminal truncation activates glp-1 protein to specify vulval fates in Caenorhabditis elegans. Nature 352, 811–815
    OpenUrlCrossRefPubMed
    1. Mango S. E.,
    2. Thorpe C. J.,
    3. Martin P. R.,
    4. Chamberlain S. H.,
    5. Bowerman B.
    (1994) Two maternal genes, apx-1 and pie-1, are required to distinguish the fates of equivalent blastomeres in the early Caenorhabditis embryo. Development 120, 2305–2315
    OpenUrlAbstract
    1. Matsunami N.,
    2. Hamaguchi Y.,
    3. Yamamoto Y.,
    4. Kuze K.,
    5. Kangawa K.,
    6. Matsuo H.,
    7. Kawaichi M.,
    8. Honjo T.
    (1989) A protein binding to the Jrecombination sequence of immunoglobulin genes contains a sequence related to the integrase motif. Nature 342, 934–937
    OpenUrlCrossRefPubMed
    1. Mello C. C.,
    2. Kramer J. M.,
    3. Stinchcomb D.,
    4. Ambros V.
    (1991) Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J 10, 3959–3970
    OpenUrlPubMedWeb of Science
    1. Mello C. C.,
    2. Draper B. W.,
    3. Priess J. R.
    (1994) The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral polarity in the early C. elegans embryo. Cell 77, 95–106
    OpenUrlCrossRefPubMedWeb of Science
    1. Moskowitz I. P. G.,
    2. Gendreau S. B.,
    3. Rothman J. H.
    (1994) Combinatorial specification of blastomere identity by glp-1 dependent cellular interactions in the nematode Caenorhabditis elegans. Development 120, 3325–3338
    OpenUrlAbstract
    1. Newman A. P.,
    2. White J. G.,
    3. Sternberg P. A.
    (1995) The Caenorhabditis elegans lin-12 gene mediates induction of ventral uterine specialization by the anchor cell. Development 121, 263–271
    OpenUrlAbstract
    1. Oka C.,
    2. Nakano T.,
    3. Wakeham A.,
    4. de la Pompa J. L.,
    5. Mori C.,
    6. Sakai T.,
    7. Okazaki S.,
    8. Kawaichi M.,
    9. Shiota K.,
    10. Mak T. W.,
    11. Honjo T.
    (1995) Disruption of the mouse RBP-J gene results in early embryonic death. Development 121, 3291–3301
    OpenUrlAbstract
    1. Otsuka A. J.,
    2. Franco R.,
    3. Yang B.,
    4. Shim K.-H.,
    5. Tang L. Z.,
    6. Zhang Y. Y.,
    7. Boontrakulpoontawee P.,
    8. Jeyaprakash A.,
    9. Hedgecock E.,
    10. Wheaton V. I.,
    11. Sobery A.
    (1995) An ankyrin-related gene (unc-44) is necessary for proper axonal guidance in Caenorhabditis elegans. J. Cell Biol 129, 1081–1092
    OpenUrlAbstract/FREE Full Text
    1. Priess J. R.,
    2. Schnabel H.,
    3. Schnabel R.
    (1987) The glp-1 locus and cellular interactions in early C. elegans embryos. Cell 51, 601–611
    OpenUrlCrossRefPubMedWeb of Science
    1. Qiao L.,
    2. Lissemore J. L.,
    3. Shu P.,
    4. Smardon A.,
    5. Gelber M. B.,
    6. Maine E. M.
    (1995) Enhancers of glp-1, a gene required for cell-signaling in Caenorhabditis elegans, define a set of genes required for germline development. Genetics 141, 551–569
    OpenUrlAbstract/FREE Full Text
    1. Schweisguth F.,
    2. Posakony J. W.
    (1992) Suppressor of Hairless, the Drosophila homolog of the mouse recombination signal-binding protein gene, controls sensory organ cell fates. Cell 69, 1199–1212
    OpenUrlCrossRefPubMedWeb of Science
    1. Seydoux G.,
    2. Greenwald I.
    (1989) Cell autonomy of lin-12 function in a cell fate decision in C. elegans. Cell 57, 1237–1245
    OpenUrlCrossRefPubMedWeb of Science
    1. Tamura K.,
    2. Taniguchi Y.,
    3. Minoguchi S.,
    4. Sakai T.,
    5. Tun T.,
    6. Furukawa T.,
    7. Honjo T.
    (1995) Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J/Su(H). Curr. Biol 5, 1416–1423
    OpenUrlCrossRefPubMedWeb of Science
    1. Tax F. E.,
    2. Yeargers J. J.,
    3. Thomas J. H.
    (1994) Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta and Serrate of Drosophila. Nature 368, 150–154
    OpenUrlCrossRefPubMed
    1. Tun T.,
    2. Hamaguchi Y.,
    3. Matsunami N.,
    4. Furukawa T.,
    5. Honjo T.,
    6. Kawaichi M.
    (1994) Recognition sequence of a highly conserved DNA binding protein RBP-J. Nucleic Acids Res 22, 965–971
    OpenUrlAbstract/FREE Full Text
    1. Waltzer L.,
    2. Logeat F.,
    3. Brou C.,
    4. Israel A.,
    5. Sergeant A.,
    6. Manet E.
    (1994) The human Jk recombination signal sequence binding protein (RBP-Jk) targets the Epstein-Barr virus EBNA2 protein to its DNA responsive elements. EMBO J 13, 5633–5638
    OpenUrlPubMedWeb of Science
    1. Wharton K. A.,
    2. Johansen K. M.,
    3. Xu T.,
    4. Artavanis-Tsakonas S.
    (1985) Nucleotide sequence from the neurogenic locus Notch implies a gene product which shares homology with proteins containing EFG-like repeats. Cell 43, 567–581
    OpenUrlCrossRefPubMedWeb of Science
    1. Wilkinson H. A.,
    2. Fitzgerald K.,
    3. Greenwald I.
    (1994) Reciprocal changes in expression of the receptor LIN-12 and its ligand LAG-2 prior to commitment in a C. elegans cell fate decision. Cell 79, 1187–1198
    OpenUrlCrossRefPubMedWeb of Science
    1. Yochem J.,
    2. Weston K.,
    3. Greenwald I.
    (1988) The Caenorhabditis elegans lin-12 gene encodes a transmembrane protein with overall similarity to Drosophila Notch. Nature 335, 547–550
    OpenUrlCrossRefPubMed
    1. Yochem J.,
    2. Greenwald I.
    (1989) glp-1 and lin-12, homologous genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane proteins. Cell 58, 553–563
    OpenUrlCrossRefPubMedWeb of Science
    1. Zimber-Strobl U.,
    2. Stroble L. J.,
    3. Meitinger C.,
    4. Hinrichs R.,
    5. Sakai T.,
    6. Furukawa T.,
    7. Honjo T.,
    8. Bornkamm G. W.
    (1994) Epstein-Barr virus nuclear antigen 2 exerts its transactivating function through interaction with recombination signal binding protein RBP-J, the homologue of Drosophila Suppressor of Hairless. EMBO J 13, 4973–4982
    OpenUrlPubMedWeb of Science
Previous ArticleNext Article
Back to top
Previous ArticleNext Article

This Issue

 Download PDF

Email

Thank you for your interest in spreading the word on Development.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H)
(Your Name) has sent you a message from Development
(Your Name) thought you would like to see the Development web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
JOURNAL ARTICLES
lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H)
S. Christensen, V. Kodoyianni, M. Bosenberg, L. Friedman, J. Kimble
Development 1996 122: 1373-1383;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
JOURNAL ARTICLES
lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H)
S. Christensen, V. Kodoyianni, M. Bosenberg, L. Friedman, J. Kimble
Development 1996 122: 1373-1383;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
  • Info & metrics
  • PDF

Related articles

Cited by...

More in this TOC section

  • Non-imprinted Igf2r expression decreases growth and rescues the Tme mutation in mice
  • REF-1, a protein with two bHLH domains, alters the pattern of cell fusion in C. elegans by regulating Hox protein activity
  • Centrosome migration into the Drosophila oocyte is independent of BicD and egl, and of the organisation of the microtubule cytoskeleton
Show more JOURNAL ARTICLES

Similar articles

Other journals from The Company of Biologists

Journal of Cell Science

Journal of Experimental Biology

Disease Models & Mechanisms

Biology Open

Advertisement

A new society for regenerative biologists

Kenneth Poss and Elly Tanaka announce the launch of the International Society for Regenerative Biology (ISRB), which will promote research and education in the field of regenerative biology.


Upcoming special issue: call for papers

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

The special issue welcomes Review articles as well as Research articles, and will be widely promoted online and at key global conferences.


An interview with Cagney Coomer

Over a virtual chat, we spoke to Cagney Coomer about her experiences in the lab, the classroom and the community centre, and why she thinks outreach and role models are vital to science.


Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.

Save your spot at our next session:

10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit

Join our mailing list to receive news and updates on the series.

Articles

  • Accepted manuscripts
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Special issues
  • Subject collections
  • Sign up for alerts

About us

  • About Development
  • About the Node
  • Editors and board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Journal Meetings
  • Workshops
  • The Company of Biologists

For authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • Biology Open transfer

Journal info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Sign up for alerts

Contact

  • Contact Development
  • Subscriptions
  • Advertising
  • Feedback
  • Institutional usage stats (logged-in users only)

 Twitter   YouTube   LinkedIn

© 2021   The Company of Biologists Ltd   Registered Charity 277992