Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. 1997 Jun; 17(6): 3345–3355.
PMCID: PMC232187

A direct contact between the dorsal rel homology domain and Twist may mediate transcriptional synergy.


The establishment of mesoderm and neuroectoderm in the early Drosophila embryo relies on interactions between the Dorsal morphogen and basic-helix-loop-helix (bHLH) activators. Here we show that Dorsal and the bHLH activator Twist synergistically activate transcription in cell culture and in vitro from a promoter containing binding sites for both factors. Somewhat surprisingly, a region of Twist outside the conserved bHLH domain is required for the synergy. In Dorsal, the rel homology domain appears to be sufficient for synergy. Protein-protein interaction assays show that Twist and Dorsal bind to one another in vitro. However, this interaction does not appear to be of sufficient strength to yield cooperative binding to DNA. Nonetheless, the regions of Twist and Dorsal required for the binding interaction are also required for synergistic transcriptional activation.

Full Text

The Full Text of this article is available as a PDF (494K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ananthan J, Baler R, Morrissey D, Zuo J, Lan Y, Weir M, Voellmy R. Synergistic activation of transcription is mediated by the N-terminal domain of Drosophila fushi tarazu homeoprotein and can occur without DNA binding by the protein. Mol Cell Biol. 1993 Mar;13(3):1599–1609. [PMC free article] [PubMed]
  • Carey M, Lin YS, Green MR, Ptashne M. A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives. Nature. 1990 May 24;345(6273):361–364. [PubMed]
  • Chi T, Carey M. The ZEBRA activation domain: modular organization and mechanism of action. Mol Cell Biol. 1993 Nov;13(11):7045–7055. [PMC free article] [PubMed]
  • Copeland JW, Nasiadka A, Dietrich BH, Krause HM. Patterning of the Drosophila embryo by a homeodomain-deleted Ftz polypeptide. Nature. 1996 Jan 11;379(6561):162–165. [PubMed]
  • Courey AJ, Huang JD. The establishment and interpretation of transcription factor gradients in the Drosophila embryo. Biochim Biophys Acta. 1995 Mar 14;1261(1):1–18. [PubMed]
  • Courey AJ, Tjian R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell. 1988 Dec 2;55(5):887–898. [PubMed]
  • Emami KH, Carey M. A synergistic increase in potency of a multimerized VP16 transcriptional activation domain. EMBO J. 1992 Dec;11(13):5005–5012. [PMC free article] [PubMed]
  • Fitzpatrick VD, Percival-Smith A, Ingles CJ, Krause HM. Homeodomain-independent activity of the fushi tarazu polypeptide in Drosophila embryos. Nature. 1992 Apr 16;356(6370):610–612. [PubMed]
  • Franzoso G, Carlson L, Brown K, Daucher MB, Bressler P, Siebenlist U. Activation of the serum response factor by p65/NF-kappaB. EMBO J. 1996 Jul 1;15(13):3403–3412. [PMC free article] [PubMed]
  • Gaub MP, Bellard M, Scheuer I, Chambon P, Sassone-Corsi P. Activation of the ovalbumin gene by the estrogen receptor involves the fos-jun complex. Cell. 1990 Dec 21;63(6):1267–1276. [PubMed]
  • González-Crespo S, Levine M. Interactions between dorsal and helix-loop-helix proteins initiate the differentiation of the embryonic mesoderm and neuroectoderm in Drosophila. Genes Dev. 1993 Sep;7(9):1703–1713. [PubMed]
  • González-Crespo S, Levine M. Related target enhancers for dorsal and NF-kappa B signaling pathways. Science. 1994 Apr 8;264(5156):255–258. [PubMed]
  • Huang JD, Schwyter DH, Shirokawa JM, Courey AJ. The interplay between multiple enhancer and silencer elements defines the pattern of decapentaplegic expression. Genes Dev. 1993 Apr;7(4):694–704. [PubMed]
  • Ip YT, Kraut R, Levine M, Rushlow CA. The dorsal morphogen is a sequence-specific DNA-binding protein that interacts with a long-range repression element in Drosophila. Cell. 1991 Jan 25;64(2):439–446. [PubMed]
  • Ip YT, Park RE, Kosman D, Bier E, Levine M. The dorsal gradient morphogen regulates stripes of rhomboid expression in the presumptive neuroectoderm of the Drosophila embryo. Genes Dev. 1992 Sep;6(9):1728–1739. [PubMed]
  • Ip YT, Park RE, Kosman D, Yazdanbakhsh K, Levine M. dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo. Genes Dev. 1992 Aug;6(8):1518–1530. [PubMed]
  • Isoda K, Roth S, Nüsslein-Volhard C. The functional domains of the Drosophila morphogen dorsal: evidence from the analysis of mutants. Genes Dev. 1992 Apr;6(4):619–630. [PubMed]
  • Jiang J, Kosman D, Ip YT, Levine M. The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos. Genes Dev. 1991 Oct;5(10):1881–1891. [PubMed]
  • Jiang J, Levine M. Binding affinities and cooperative interactions with bHLH activators delimit threshold responses to the dorsal gradient morphogen. Cell. 1993 Mar 12;72(5):741–752. [PubMed]
  • Kadonaga JT, Tjian R. Affinity purification of sequence-specific DNA binding proteins. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5889–5893. [PMC free article] [PubMed]
  • Kasai Y, Nambu JR, Lieberman PM, Crews ST. Dorsal-ventral patterning in Drosophila: DNA binding of snail protein to the single-minded gene. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3414–3418. [PMC free article] [PubMed]
  • Kieran M, Blank V, Logeat F, Vandekerckhove J, Lottspeich F, Le Bail O, Urban MB, Kourilsky P, Baeuerle PA, Israël A. The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. Cell. 1990 Sep 7;62(5):1007–1018. [PubMed]
  • Kosman D, Ip YT, Levine M, Arora K. Establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo. Science. 1991 Oct 4;254(5028):118–122. [PubMed]
  • Leptin M. twist and snail as positive and negative regulators during Drosophila mesoderm development. Genes Dev. 1991 Sep;5(9):1568–1576. [PubMed]
  • Liaw GJ. Improved protocol for directional multimerization of a DNA fragment. Biotechniques. 1994 Oct;17(4):668–670. [PubMed]
  • Lin YS, Carey M, Ptashne M, Green MR. How different eukaryotic transcriptional activators can cooperate promiscuously. Nature. 1990 May 24;345(6273):359–361. [PubMed]
  • Molkentin JD, Black BL, Martin JF, Olson EN. Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell. 1995 Dec 29;83(7):1125–1136. [PubMed]
  • Pan DJ, Huang JD, Courey AJ. Functional analysis of the Drosophila twist promoter reveals a dorsal-binding ventral activator region. Genes Dev. 1991 Oct;5(10):1892–1901. [PubMed]
  • Roth S, Stein D, Nüsslein-Volhard C. A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo. Cell. 1989 Dec 22;59(6):1189–1202. [PubMed]
  • Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Mar 22;251(5000):1490–1493. [PubMed]
  • Rushlow C, Frasch M, Doyle H, Levine M. Maternal regulation of zerknüllt: a homoeobox gene controlling differentiation of dorsal tissues in Drosophila. Nature. 1987 Dec 10;330(6148):583–586. [PubMed]
  • Rushlow C, Warrior R. The rel family of proteins. Bioessays. 1992 Feb;14(2):89–95. [PubMed]
  • Rushlow CA, Han K, Manley JL, Levine M. The graded distribution of the dorsal morphogen is initiated by selective nuclear transport in Drosophila. Cell. 1989 Dec 22;59(6):1165–1177. [PubMed]
  • Sauer F, Hansen SK, Tjian R. Multiple TAFIIs directing synergistic activation of transcription. Science. 1995 Dec 15;270(5243):1783–1788. [PubMed]
  • Sheldon M, Reinberg D. Transcriptional activation. Tuning-up transcription. Curr Biol. 1995 Jan 1;5(1):43–46. [PubMed]
  • Siebenlist U, Franzoso G, Brown K. Structure, regulation and function of NF-kappa B. Annu Rev Cell Biol. 1994;10:405–455. [PubMed]
  • Simpson P. Maternal-Zygotic Gene Interactions during Formation of the Dorsoventral Pattern in Drosophila Embryos. Genetics. 1983 Nov;105(3):615–632. [PMC free article] [PubMed]
  • Steward R. Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. Science. 1987 Oct 30;238(4827):692–694. [PubMed]
  • Steward R. Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function. Cell. 1989 Dec 22;59(6):1179–1188. [PubMed]
  • St Johnston RD, Gelbart WM. Decapentaplegic transcripts are localized along the dorsal-ventral axis of the Drosophila embryo. EMBO J. 1987 Sep;6(9):2785–2791. [PMC free article] [PubMed]
  • Szymanski P, Levine M. Multiple modes of dorsal-bHLH transcriptional synergy in the Drosophila embryo. EMBO J. 1995 May 15;14(10):2229–2238. [PMC free article] [PubMed]
  • Thisse C, Perrin-Schmitt F, Stoetzel C, Thisse B. Sequence-specific transactivation of the Drosophila twist gene by the dorsal gene product. Cell. 1991 Jun 28;65(7):1191–1201. [PubMed]
  • Thisse B, Stoetzel C, Gorostiza-Thisse C, Perrin-Schmitt F. Sequence of the twist gene and nuclear localization of its protein in endomesodermal cells of early Drosophila embryos. EMBO J. 1988 Jul;7(7):2175–2183. [PMC free article] [PubMed]
  • Urban MB, Baeuerle PA. The 65-kD subunit of NF-kappa B is a receptor for I kappa B and a modulator of DNA-binding specificity. Genes Dev. 1990 Nov;4(11):1975–1984. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...