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Gene Review

Dref  -  DNA replication-related element factor

Drosophila melanogaster

Synonyms: CG5838, DREF, DmDREF, Dmel\CG5838, Dmel_DREF, ...
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Disease relevance of Dref


High impact information on Dref

  • TRF2 associates with DREF and directs promoter-selective gene expression in Drosophila [2].
  • In conditions of suppressed apoptosis, DREF activation can cause overgrowth of developing organs [3].
  • These data establish DREF as a global regulator of transcriptional programs that mediate cell proliferation and organ growth during animal development [3].
  • DREF is required for efficient growth and cell cycle progression in Drosophila imaginal discs [3].
  • We show that DREF regulates the expression of genes that are required for the transition of imaginal disc cells through S phase [3].

Biological context of Dref


Anatomical context of Dref

  • While the effects on the mutation in the DNA replication-related element (DRE) in cultured cells have been studied extensively, the consequences of elevating wild-type DREF activity in developing tissues have hitherto remained unclear [6].
  • Expression of DREF induced ectopic DNA synthesis in the cells behind the morphogenetic furrow, which are normally postmitotic, and abolished photoreceptor specifications of R1, R6, and R7 [7].

Associations of Dref with chemical compounds

  • Chromatin immunoprecipitation assays in the presence or absence of 20-hydroxyecdysone further showed both DREF and Cut proteins to be localized in the genomic region containing the dPCNA promoter in S2 cells, especially in the Cut case upon induction of differentiation [8].
  • Deduced from the nucleotide sequences of cDNA, DREF is a polypeptide of 701 amino acid residues with a molecular weight of 80,096, which contains three characteristic regions, rich in basic amino acids, proline, and acidic amino acids, respectively [9].
  • Here, we report that the DNA binding activity of DREF is regulated by a redox mechanism, and that the cysteine residues are involved in this regulation [10].
  • Using DRE-conjugated latex particles, DREF was affinity-purified from the Kc cell nuclear extract [11].

Physical interactions of Dref


Regulatory relationships of Dref

  • Here we show Zen downregulates DREF gene promoter activity through action on the region between +241 and +254 (5'-AGAATACTCAACA) [4].
  • Drosophila Mi-2 negatively regulates dDREF by inhibiting its DNA-binding activity [5].
  • The data suggest that transcription of the D-mtTFA gene is under control of the DRE/DREF regulatory system [12].
  • A half reduction of the reaper, head involution defective and grim gene dose suppressed this DREF-induced notching wing phenotype [6].
  • Our data suggest strongly that the Drosophila mtSSB gene is regulated by the DRE/DREF system [14].

Other interactions of Dref

  • Using a specific antibody against the dMLF, we performed immunofluorescent staining of Drosophila Kc cells and showed a primarily cytoplasmic staining, whereas DREF localizes in the nucleus [1].
  • The protein is enriched in replicating tissues, and consistent with this the region upstream of the gene contains close matches to the sites of two transcription factors - Dref and E2f - which have been implicated in controlling proliferation-associated genes [15].
  • To our knowledge, this is the first evidence for a genetic interaction between DREF and BEAF-32 [6].
  • Antagonistic regulation of the Drosophila PCNA gene promoter by DREF and Cut [8].
  • Drosophila damage-specific DNA-binding protein 1 (D-DDB1) is controlled by the DRE/DREF system [16].

Analytical, diagnostic and therapeutic context of Dref

  • Electrophoretic mobility shift assays showed that dMi-2 thereby inhibits the DNA-binding activity of dDREF [5].
  • Genetic crosses of transgenic flies expressing DREF to a collection of Drosophila deficiency stocks allowed us to identify several genomic regions, deletions of which caused enhancement or suppression of the DREF-induced rough eye phenotype [7].
  • We used site-directed mutagenesis and in vitro transient transfection assays to establish that expression of the catalase gene is regulated by DREF through the DRE site [13].
  • On gel filtration chromatography, a single peak of DREF activity was recovered in fractions corresponding to a molecular mass of 170 kDa, and the 86-kDa polypeptide was detected only in the corresponding fractions; thus, active DREF is probably a homodimeric form of the 86-kDa polypeptide [11].
  • Monoclonal antibodies against Drosophila DREF inhibited the binding activity of the factor, as shown by gel mobility shift assays, and allowed specific detection of a 100 kDa protein on immuno Western blot analysis [17].


  1. Characterization of a Drosophila homologue of the human myelodysplasia/myeloid leukemia factor (MLF). Ohno, K., Takahashi, Y., Hirose, F., Inoue, Y.H., Taguchi, O., Nishida, Y., Matsukage, A., Yamaguchi, M. Gene (2000) [Pubmed]
  2. TRF2 associates with DREF and directs promoter-selective gene expression in Drosophila. Hochheimer, A., Zhou, S., Zheng, S., Holmes, M.C., Tjian, R. Nature (2002) [Pubmed]
  3. DREF is required for efficient growth and cell cycle progression in Drosophila imaginal discs. Hyun, J., Jasper, H., Bohmann, D. Mol. Cell. Biol. (2005) [Pubmed]
  4. Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis. Kwon, E., Seto, H., Hirose, F., Ohshima, N., Takahashi, Y., Nishida, Y., Yamaguchi, M. Gene (2003) [Pubmed]
  5. Drosophila Mi-2 negatively regulates dDREF by inhibiting its DNA-binding activity. Hirose, F., Ohshima, N., Kwon, E.J., Yoshida, H., Yamaguchi, M. Mol. Cell. Biol. (2002) [Pubmed]
  6. Over-expression of DREF in the Drosophila wing imaginal disc induces apoptosis and a notching wing phenotype. Yoshida, H., Inoue, Y.H., Hirose, F., Sakaguchi, K., Matsukage, A., Yamaguchi, M. Genes Cells (2001) [Pubmed]
  7. Ectopic expression of DREF induces DNA synthesis, apoptosis, and unusual morphogenesis in the Drosophila eye imaginal disc: possible interaction with Polycomb and trithorax group proteins. Hirose, F., Ohshima, N., Shiraki, M., Inoue, Y.H., Taguchi, O., Nishi, Y., Matsukage, A., Yamaguchi, M. Mol. Cell. Biol. (2001) [Pubmed]
  8. Antagonistic regulation of the Drosophila PCNA gene promoter by DREF and Cut. Seto, H., Hayashi, Y., Kwon, E., Taguchi, O., Yamaguchi, M. Genes Cells (2006) [Pubmed]
  9. Isolation and characterization of cDNA for DREF, a promoter-activating factor for Drosophila DNA replication-related genes. Hirose, F., Yamaguchi, M., Kuroda, K., Omori, A., Hachiya, T., Ikeda, M., Nishimoto, Y., Matsukage, A. J. Biol. Chem. (1996) [Pubmed]
  10. Redox regulation of DNA binding activity of DREF (DNA replication-related element binding factor) in Drosophila. Choi, T.Y., Park, S.Y., Kang, H.S., Cheong, J.H., Kim, H.D., Lee, B.L., Hirose, F., Yamaguchi, M., Yoo, M.A. Biochem. J. (2004) [Pubmed]
  11. Novel 8-base pair sequence (Drosophila DNA replication-related element) and specific binding factor involved in the expression of Drosophila genes for DNA polymerase alpha and proliferating cell nuclear antigen. Hirose, F., Yamaguchi, M., Handa, H., Inomata, Y., Matsukage, A. J. Biol. Chem. (1993) [Pubmed]
  12. Drosophila mitochondrial transcription factor A: characterization of its cDNA and expression pattern during development. Takata, K., Yoshida, H., Hirose, F., Yamaguchi, M., Kai, M., Oshige, M., Sakimoto, I., Koiwai, O., Sakaguchi, K. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  13. Transcriptional regulation of the Drosophila catalase gene by the DRE/DREF system. Park, S.Y., Kim, Y.S., Yang, D.J., Yoo, M.A. Nucleic Acids Res. (2004) [Pubmed]
  14. Regulation of mitochondrial single-stranded DNA-binding protein gene expression links nuclear and mitochondrial DNA replication in drosophila. Ruiz De Mena, I., Lefai, E., Garesse, R., Kaguni, L.S. J. Biol. Chem. (2000) [Pubmed]
  15. Cloning and characterisation of the gene for the large subunit of the DNA primase from Drosophila melanogaster. Huikeshoven, H., Cotterill, S. Biochim. Biophys. Acta (1999) [Pubmed]
  16. Drosophila damage-specific DNA-binding protein 1 (D-DDB1) is controlled by the DRE/DREF system. Takata, K., Ishikawa, G., Hirose, F., Sakaguchi, K. Nucleic Acids Res. (2002) [Pubmed]
  17. Involvement of the DNA replication-related element (DRE) and DRE-binding factor (DREF) in transcriptional regulation of the Bombyx mori PCNA gene. Takahashi, Y., Yamaguchi, M., Hirose, F., Kobayashi, J., Miyajima, S., Matsukage, A. J. Biochem. (1997) [Pubmed]
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