Logo of embojLink to Publisher's site
EMBO J. 1996 Apr 15; 15(8): 1961–1970.
PMCID: PMC450115

DEAF-1, a novel protein that binds an essential region in a Deformed response element.


A 120 bp homeotic response element that is regulated specifically by Deformed in Drosophila embryos contains a single binding site for Deformed protein. However, a 24 bp sub-element containing this site does not constitute a Deformed response element. Specific activation requires a second region in the 120 bp element, which presumably contains one or more binding sites for Deformed cofactors. We have isolated a novel protein from Drosophila nuclear extracts which binds specifically to a site in this second region. This protein, which we call DEAF-1 (Deformed epidermal autoregulatory factor-1), contains three conserved domains. One of these includes a cysteine repeat motif that is similar to a motif found in Drosophila Nervy and the human MTG8 proto-oncoprotein, and another matches a region of Drosophila Trithorax. Mutations in the response element designed to improve binding to DEAF-1 in vitro resulted in increased embryonic expression. Conversely, small mutations designed to diminish binding to DEAF-1 resulted in reduced expression of the element. Thus, DEAF-1 is likely to contribute to the functional activity, and perhaps to the homeotic specificity, of this response element. Consistent with this hypothesis, we have discovered DEAF-1 binding sites in other Deformed response elements.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Affolter M, Percival-Smith A, Müller M, Leupin W, Gehring WJ. DNA binding properties of the purified Antennapedia homeodomain. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4093–4097. [PMC free article] [PubMed]
  • Biggin MD, Tjian R. Transcription factors that activate the Ultrabithorax promoter in developmentally staged extracts. Cell. 1988 Jun 3;53(5):699–711. [PubMed]
  • Brown NH, Kafatos FC. Functional cDNA libraries from Drosophila embryos. J Mol Biol. 1988 Sep 20;203(2):425–437. [PubMed]
  • Chadwick R, McGinnis W. Temporal and spatial distribution of transcripts from the Deformed gene of Drosophila. EMBO J. 1987 Mar;6(3):779–789. [PMC free article] [PubMed]
  • Chan SK, Jaffe L, Capovilla M, Botas J, Mann RS. The DNA binding specificity of Ultrabithorax is modulated by cooperative interactions with extradenticle, another homeoprotein. Cell. 1994 Aug 26;78(4):603–615. [PubMed]
  • Chang CP, Shen WF, Rozenfeld S, Lawrence HJ, Largman C, Cleary ML. Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins. Genes Dev. 1995 Mar 15;9(6):663–674. [PubMed]
  • Desplan C, Theis J, O'Farrell PH. The sequence specificity of homeodomain-DNA interaction. Cell. 1988 Sep 23;54(7):1081–1090. [PMC free article] [PubMed]
  • Dessain S, Gross CT, Kuziora MA, McGinnis W. Antp-type homeodomains have distinct DNA binding specificities that correlate with their different regulatory functions in embryos. EMBO J. 1992 Mar;11(3):991–1002. [PMC free article] [PubMed]
  • Ekker SC, Jackson DG, von Kessler DP, Sun BI, Young KE, Beachy PA. The degree of variation in DNA sequence recognition among four Drosophila homeotic proteins. EMBO J. 1994 Aug 1;13(15):3551–3560. [PMC free article] [PubMed]
  • Elfring LK, Deuring R, McCallum CM, Peterson CL, Tamkun JW. Identification and characterization of Drosophila relatives of the yeast transcriptional activator SNF2/SWI2. Mol Cell Biol. 1994 Apr;14(4):2225–2234. [PMC free article] [PubMed]
  • Erickson PF, Robinson M, Owens G, Drabkin HA. The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a highly evolutionarily conserved, putative transcription factor. Cancer Res. 1994 Apr 1;54(7):1782–1786. [PubMed]
  • Feinstein PG, Kornfeld K, Hogness DS, Mann RS. Identification of homeotic target genes in Drosophila melanogaster including nervy, a proto-oncogene homologue. Genetics. 1995 Jun;140(2):573–586. [PMC free article] [PubMed]
  • Florence B, Handrow R, Laughon A. DNA-binding specificity of the fushi tarazu homeodomain. Mol Cell Biol. 1991 Jul;11(7):3613–3623. [PMC free article] [PubMed]
  • Hanes SD, Riddihough G, Ish-Horowicz D, Brent R. Specific DNA recognition and intersite spacing are critical for action of the bicoid morphogen. Mol Cell Biol. 1994 May;14(5):3364–3375. [PMC free article] [PubMed]
  • Hatfull GF, Grindley ND. Analysis of gamma delta resolvase mutants in vitro: evidence for an interaction between serine-10 of resolvase and site I of res. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5429–5433. [PMC free article] [PubMed]
  • Hoey T, Levine M. Divergent homeo box proteins recognize similar DNA sequences in Drosophila. Nature. 1988 Apr 28;332(6167):858–861. [PubMed]
  • Johnson FB, Parker E, Krasnow MA. Extradenticle protein is a selective cofactor for the Drosophila homeotics: role of the homeodomain and YPWM amino acid motif in the interaction. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):739–743. [PMC free article] [PubMed]
  • Kadereit S, Gewert DR, Galabru J, Hovanessian AG, Meurs EF. Molecular cloning of two new interferon-induced, highly related nuclear phosphoproteins. J Biol Chem. 1993 Nov 15;268(32):24432–24441. [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]
  • Kennison JA. Transcriptional activation of Drosophila homeotic genes from distant regulatory elements. Trends Genet. 1993 Mar;9(3):75–79. [PubMed]
  • Kennison JA, Tamkun JW. Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8136–8140. [PMC free article] [PubMed]
  • Kenyon C. If birds can fly, why can't we? Homeotic genes and evolution. Cell. 1994 Jul 29;78(2):175–180. [PubMed]
  • Mahaffey JW, Jones DF, Hickel JA, Griswold CM. Identification and characterization of a gene activated by the deformed homeoprotein. Development. 1993 May;118(1):203–214. [PubMed]
  • Malicki J, Cianetti LC, Peschle C, McGinnis W. A human HOX4B regulatory element provides head-specific expression in Drosophila embryos. Nature. 1992 Jul 23;358(6384):345–347. [PubMed]
  • Mazo AM, Huang DH, Mozer BA, Dawid IB. The trithorax gene, a trans-acting regulator of the bithorax complex in Drosophila, encodes a protein with zinc-binding domains. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2112–2116. [PMC free article] [PubMed]
  • McGinnis W, Krumlauf R. Homeobox genes and axial patterning. Cell. 1992 Jan 24;68(2):283–302. [PubMed]
  • Merrill VK, Turner FR, Kaufman TC. A genetic and developmental analysis of mutations in the Deformed locus in Drosophila melanogaster. Dev Biol. 1987 Aug;122(2):379–395. [PubMed]
  • Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J. 1993 Jul;12(7):2715–2721. [PMC free article] [PubMed]
  • Mohler J, Mahaffey JW, Deutsch E, Vani K. Control of Drosophila head segment identity by the bZIP homeotic gene cnc. Development. 1995 Jan;121(1):237–247. [PubMed]
  • Owens GP, Hahn WE, Cohen JJ. Identification of mRNAs associated with programmed cell death in immature thymocytes. Mol Cell Biol. 1991 Aug;11(8):4177–4188. [PMC free article] [PubMed]
  • Peifer M, Wieschaus E. Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity. Genes Dev. 1990 Jul;4(7):1209–1223. [PubMed]
  • Pöpperl H, Bienz M, Studer M, Chan SK, Aparicio S, Brenner S, Mann RS, Krumlauf R. Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Cell. 1995 Jun 30;81(7):1031–1042. [PubMed]
  • Regulski M, McGinnis N, Chadwick R, McGinnis W. Developmental and molecular analysis of Deformed; a homeotic gene controlling Drosophila head development. EMBO J. 1987 Mar;6(3):767–777. [PMC free article] [PubMed]
  • Schier AF, Gehring WJ. Analysis of a fushi tarazu autoregulatory element: multiple sequence elements contribute to enhancer activity. EMBO J. 1993 Mar;12(3):1111–1119. [PMC free article] [PubMed]
  • Schwabe JW, Klug A. Zinc mining for protein domains. Nat Struct Biol. 1994 Jun;1(6):345–349. [PubMed]
  • Sedkov Y, Tillib S, Mizrokhi L, Mazo A. The bithorax complex is regulated by trithorax earlier during Drosophila embryogenesis than is the Antennapedia complex, correlating with a bithorax-like expression pattern of distinct early trithorax transcripts. Development. 1994 Jul;120(7):1907–1917. [PubMed]
  • Smith DL, Johnson AD. A molecular mechanism for combinatorial control in yeast: MCM1 protein sets the spacing and orientation of the homeodomains of an alpha 2 dimer. Cell. 1992 Jan 10;68(1):133–142. [PubMed]
  • Tautz D, Pfeifle C. A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback. Chromosoma. 1989 Aug;98(2):81–85. [PubMed]
  • Tripoulas NA, Hersperger E, La Jeunesse D, Shearn A. Molecular genetic analysis of the Drosophila melanogaster gene absent, small or homeotic discs1 (ash1). Genetics. 1994 Aug;137(4):1027–1038. [PMC free article] [PubMed]
  • van Dijk MA, Murre C. extradenticle raises the DNA binding specificity of homeotic selector gene products. Cell. 1994 Aug 26;78(4):617–624. [PubMed]
  • Vincent JP, Kassis JA, O'Farrell PH. A synthetic homeodomain binding site acts as a cell type specific, promoter specific enhancer in Drosophila embryos. EMBO J. 1990 Aug;9(8):2573–2578. [PMC free article] [PubMed]
  • Walker S, Hayes S, O'Hare P. Site-specific conformational alteration of the Oct-1 POU domain-DNA complex as the basis for differential recognition by Vmw65 (VP16). Cell. 1994 Dec 2;79(5):841–852. [PubMed]
  • Walter J, Dever CA, Biggin MD. Two homeo domain proteins bind with similar specificity to a wide range of DNA sites in Drosophila embryos. Genes Dev. 1994 Jul 15;8(14):1678–1692. [PubMed]
  • Zeng C, Pinsonneault J, Gellon G, McGinnis N, McGinnis W. Deformed protein binding sites and cofactor binding sites are required for the function of a small segment-specific regulatory element in Drosophila embryos. EMBO J. 1994 May 15;13(10):2362–2377. [PMC free article] [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Conserved Domains
    Conserved Domains
    Link to related CDD entry
  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...