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. 1991 Jun 15;88(12):5388–5392. doi: 10.1073/pnas.88.12.5388

Several regions of Antennapedia and thyroid transcription factor 1 homeodomains contribute to DNA binding specificity.

G Damante 1, R Di Lauro 1
PMCID: PMC51878  PMID: 1675795

Abstract

The DNA binding specificities of the homeodomains contained in thyroid transcription factor 1 and Antennapedia have been compared. The two homeodomains recognize different DNA sequences, despite the similar amino acid sequences of their recognition helix. Mutations that make the recognition helix of thyroid transcription factor 1 identical to the one contained in Antennapedia have no effects on the binding specificity of thyroid transcription factor 1. The exchange of other segments between these two homeodomains allows the identification of the regions responsible for the observed DNA binding specificities. These results indicate that amino acid residues outside of the recognition helix play an important role in the determination of the DNA binding specificities of these two homeodomains.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Affolter M., Percival-Smith A., Müller M., Leupin W., Gehring W. J. DNA binding properties of the purified Antennapedia homeodomain. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4093–4097. doi: 10.1073/pnas.87.11.4093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Affolter M., Schier A., Gehring W. J. Homeodomain proteins and the regulation of gene expression. Curr Opin Cell Biol. 1990 Jun;2(3):485–495. doi: 10.1016/0955-0674(90)90132-x. [DOI] [PubMed] [Google Scholar]
  3. Baumruker T., Sturm R., Herr W. OBP100 binds remarkably degenerate octamer motifs through specific interactions with flanking sequences. Genes Dev. 1988 Nov;2(11):1400–1413. doi: 10.1101/gad.2.11.1400. [DOI] [PubMed] [Google Scholar]
  4. Desplan C., Theis J., O'Farrell P. H. The sequence specificity of homeodomain-DNA interaction. Cell. 1988 Sep 23;54(7):1081–1090. doi: 10.1016/0092-8674(88)90123-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. García-Blanco M. A., Clerc R. G., Sharp P. A. The DNA-binding homeo domain of the Oct-2 protein. Genes Dev. 1989 Jun;3(6):739–745. doi: 10.1101/gad.3.6.739. [DOI] [PubMed] [Google Scholar]
  6. Gehring W. J., Müller M., Affolter M., Percival-Smith A., Billeter M., Qian Y. Q., Otting G., Wüthrich K. The structure of the homeodomain and its functional implications. Trends Genet. 1990 Oct;6(10):323–329. doi: 10.1016/0168-9525(90)90253-3. [DOI] [PubMed] [Google Scholar]
  7. Guazzi S., Price M., De Felice M., Damante G., Mattei M. G., Di Lauro R. Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity. EMBO J. 1990 Nov;9(11):3631–3639. doi: 10.1002/j.1460-2075.1990.tb07574.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hanes S. D., Brent R. A genetic model for interaction of the homeodomain recognition helix with DNA. Science. 1991 Jan 25;251(4992):426–430. doi: 10.1126/science.1671176. [DOI] [PubMed] [Google Scholar]
  9. Hanes S. D., Brent R. DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9. Cell. 1989 Jun 30;57(7):1275–1283. doi: 10.1016/0092-8674(89)90063-9. [DOI] [PubMed] [Google Scholar]
  10. Hoey T., Levine M. Divergent homeo box proteins recognize similar DNA sequences in Drosophila. Nature. 1988 Apr 28;332(6167):858–861. doi: 10.1038/332858a0. [DOI] [PubMed] [Google Scholar]
  11. Hoey T., Warrior R., Manak J., Levine M. DNA-binding activities of the Drosophila melanogaster even-skipped protein are mediated by its homeo domain and influenced by protein context. Mol Cell Biol. 1988 Nov;8(11):4598–4607. doi: 10.1128/mcb.8.11.4598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Horton R. M., Hunt H. D., Ho S. N., Pullen J. K., Pease L. R. Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene. 1989 Apr 15;77(1):61–68. doi: 10.1016/0378-1119(89)90359-4. [DOI] [PubMed] [Google Scholar]
  13. Ingraham H. A., Flynn S. E., Voss J. W., Albert V. R., Kapiloff M. S., Wilson L., Rosenfeld M. G. The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions. Cell. 1990 Jun 15;61(6):1021–1033. doi: 10.1016/0092-8674(90)90067-o. [DOI] [PubMed] [Google Scholar]
  14. Kim Y., Nirenberg M. Drosophila NK-homeobox genes. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7716–7720. doi: 10.1073/pnas.86.20.7716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kissinger C. R., Liu B. S., Martin-Blanco E., Kornberg T. B., Pabo C. O. Crystal structure of an engrailed homeodomain-DNA complex at 2.8 A resolution: a framework for understanding homeodomain-DNA interactions. Cell. 1990 Nov 2;63(3):579–590. doi: 10.1016/0092-8674(90)90453-l. [DOI] [PubMed] [Google Scholar]
  16. Kuziora M. A., McGinnis W. A homeodomain substitution changes the regulatory specificity of the deformed protein in Drosophila embryos. Cell. 1989 Nov 3;59(3):563–571. doi: 10.1016/0092-8674(89)90039-1. [DOI] [PubMed] [Google Scholar]
  17. Laughon A., Scott M. P. Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins. Nature. 1984 Jul 5;310(5972):25–31. doi: 10.1038/310025a0. [DOI] [PubMed] [Google Scholar]
  18. Mihara H., Kaiser E. T. A chemically synthesized Antennapedia homeo domain binds to a specific DNA sequence. Science. 1988 Nov 11;242(4880):925–927. doi: 10.1126/science.2903553. [DOI] [PubMed] [Google Scholar]
  19. Müller M., Affolter M., Leupin W., Otting G., Wüthrich K., Gehring W. J. Isolation and sequence-specific DNA binding of the Antennapedia homeodomain. EMBO J. 1988 Dec 20;7(13):4299–4304. doi: 10.1002/j.1460-2075.1988.tb03328.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Otting G., Qian Y. Q., Billeter M., Müller M., Affolter M., Gehring W. J., Wüthrich K. Protein--DNA contacts in the structure of a homeodomain--DNA complex determined by nuclear magnetic resonance spectroscopy in solution. EMBO J. 1990 Oct;9(10):3085–3092. doi: 10.1002/j.1460-2075.1990.tb07505.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Otting G., Qian Y. Q., Müller M., Affolter M., Gehring W., Wüthrich K. Secondary structure determination for the Antennapedia homeodomain by nuclear magnetic resonance and evidence for a helix-turn-helix motif. EMBO J. 1988 Dec 20;7(13):4305–4309. doi: 10.1002/j.1460-2075.1988.tb03329.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Percival-Smith A., Müller M., Affolter M., Gehring W. J. The interaction with DNA of wild-type and mutant fushi tarazu homeodomains. EMBO J. 1990 Dec;9(12):3967–3974. doi: 10.1002/j.1460-2075.1990.tb07617.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pick L., Schier A., Affolter M., Schmidt-Glenewinkel T., Gehring W. J. Analysis of the ftz upstream element: germ layer-specific enhancers are independently autoregulated. Genes Dev. 1990 Jul;4(7):1224–1239. doi: 10.1101/gad.4.7.1224. [DOI] [PubMed] [Google Scholar]
  24. Qian Y. Q., Billeter M., Otting G., Müller M., Gehring W. J., Wüthrich K. The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: comparison with prokaryotic repressors. Cell. 1989 Nov 3;59(3):573–580. doi: 10.1016/0092-8674(89)90040-8. [DOI] [PubMed] [Google Scholar]
  25. Ruvkun G., Finney M. Regulation of transcription and cell identity by POU domain proteins. Cell. 1991 Feb 8;64(3):475–478. doi: 10.1016/0092-8674(91)90227-p. [DOI] [PubMed] [Google Scholar]
  26. Sarkar G., Sommer S. S. The "megaprimer" method of site-directed mutagenesis. Biotechniques. 1990 Apr;8(4):404–407. [PubMed] [Google Scholar]
  27. Scott M. P., Tamkun J. W., Hartzell G. W., 3rd The structure and function of the homeodomain. Biochim Biophys Acta. 1989 Jul 28;989(1):25–48. doi: 10.1016/0304-419x(89)90033-4. [DOI] [PubMed] [Google Scholar]
  28. Shepherd J. C., McGinnis W., Carrasco A. E., De Robertis E. M., Gehring W. J. Fly and frog homoeo domains show homologies with yeast mating type regulatory proteins. Nature. 1984 Jul 5;310(5972):70–71. doi: 10.1038/310070a0. [DOI] [PubMed] [Google Scholar]
  29. Treisman J., Gönczy P., Vashishtha M., Harris E., Desplan C. A single amino acid can determine the DNA binding specificity of homeodomain proteins. Cell. 1989 Nov 3;59(3):553–562. doi: 10.1016/0092-8674(89)90038-x. [DOI] [PubMed] [Google Scholar]
  30. Verrijzer C. P., Kal A. J., van der Vliet P. C. The oct-1 homeo domain contacts only part of the octamer sequence and full oct-1 DNA-binding activity requires the POU-specific domain. Genes Dev. 1990 Nov;4(11):1964–1974. doi: 10.1101/gad.4.11.1964. [DOI] [PubMed] [Google Scholar]

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