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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Identification of a Novel Human Zinc Finger Gene, ZNF438, with Transcription Inhibition Activity

  • Zhong, Zhaomin (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Wan, Bo (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Qiu, Yun (Anesthesiology Department, Suzhou Yongding Hospital) ;
  • Ni, Jun (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Tang, Wenwen (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Chen, Xinya (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Yang, Yun (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Shen, Suqin (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Wang, Ying (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Bai, Meirong (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Lang, Qingyu (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University) ;
  • Yu, Long (State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University)
  • Published : 2007.07.31
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Abstract

There were many different families of zinc finger proteins that contained multiple cysteine and/or histidine residues and used zinc to stabilize their folds. The classical C2H2 zinc finger proteins were the founding members of this superfamily and were among the most abundant proteins in eukaryotic genomes. C2H2 proteins typically contained several C2H2 fingers that made tandem contacts along the DNA. Here we reported a novel C2H2 type zinc finger gene, ZNF438, which encoded 828 amino acids that formed five zinc finger domains. Bioinformatics analysis revealed that the ZNF438 was mapped to human chromosome 10p11.2 and shared 62% identity with rat and mouse homologues. RT-PCR analysis indicated that it was ubiquitously expressed in 18 human adult tissues. With immunofluorescence assay, it was shown that the exogenous Flag-tagged ZNF438 was located in nucleus of COS-7 cells. To further explore the function of ZNF438, we examined the transcriptional activity of ZNF438 protein by transfecting recombinant pM-ZNF438 into mammalian cells. The subsequent analysis based on the duel luciferase assay system showed that ZNF438 was a transcriptional repressor.

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References

  1. Bardwell, V. J. and Treisman, R. (1994) The POZ domain: a conserved protein-protein interaction motif. Genes Dev. 8, 1664-1677. https://doi.org/10.1101/gad.8.14.1664
  2. Bellefroid, E. J., Marine, J. C., Ried, T., Lecocq, P. J., Riviere, M., Amemiya, C., Poncelet, D. A., Coulie, P. G., de Jong, P., Szpirer, C., Ward, D. C. and Martial, J. A. (1993) Clustered organization of homologous KRAB zinc-finger genes with enhanced expression in human T lymphoid cells. EMBO J. 12, 1363-1374.
  3. Brown, R. S., Sander, C. and Argos, P. (1985) The primary structure of transcription factor TFIIIA has 12 consecutive repeats. FEBS Lett. 186, 271-276. https://doi.org/10.1016/0014-5793(85)80723-7
  4. Busch, S. J. and Sassone-Corsi, P. (1990) Dimers, leucine zippers and DNA-binding domains. Trends Genet. 6, 36-40. https://doi.org/10.1016/0168-9525(90)90071-D
  5. De Luca, P., Majello, B. and Lania, L. (1996) Sp3 represses transcription when tethered to promoter DNA or targeted to promoter proximal RNA. J. Biol. Chem. 271, 8533-8536. https://doi.org/10.1074/jbc.271.15.8533
  6. Gostissa, M., Hengstermann, A., Fogal, V., Sandy, P., Schwarz, S. E., Scheffner, M. and Del Sal, G. (1999) Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. EMBO J. 18, 6462-6471. https://doi.org/10.1093/emboj/18.22.6462
  7. Grishin, N. V. (2001) Treble clef finger-a functionally diverse zinc-binding structural motif. Nucleic Acids Res. 29, 1703-1714. https://doi.org/10.1093/nar/29.8.1703
  8. Hagen, G., Muller, S., Beato, M. and Suske, G. (1994) Sp1-mediated transcriptional activation is repressed by Sp3. EMBO J. 13, 3843-3851.
  9. Han, Z. G., Zhang, Q. H., Ye, M., Kan, L. X., Gu, B. W., He, K. L., Shi, S. L., Zhou, J., Fu, G., Mao, M., Chen, S. J., Yu, L. and Chen, Z. (1999) Molecular cloning of six novel Kruppellike zinc finger genes from hematopoietic cells and identification of a novel transregulatory domain KRNB. J. Biol. Chem. 274, 35741-35748. https://doi.org/10.1074/jbc.274.50.35741
  10. Knochel, W., Poting, A., Koster, M., el Baradi, T., Nietfeld, W., Bouwmeester, T. and Pieler, T. (1989) Evolutionary conserved modules associated with zinc fingers in Xenopus laevis. Proc. Natl. Acad. Sci. USA 86, 6097-6100. https://doi.org/10.1073/pnas.86.16.6097
  11. Krishna, S. S., Majumdar, I. and Grishin, N. V. (2003) Structural classification of zinc fingers: survey and summary. Nucleic Acids Res. 31, 532-550. https://doi.org/10.1093/nar/gkg161
  12. Kumar, A. P. and Butler, A. P. (1997) Transcription factor Sp3 antagonizes activation of the ornithine decarboxylase promoter by Sp1. Nucleic Acids Res. 25, 2012-2019. https://doi.org/10.1093/nar/25.10.2012
  13. Lania, L., Majello, B. and De Luca, P. (1997) Transcriptional regulation by the Sp family proteins. Int. J. Biochem. Cell. Biol. 29, 1313-1323. https://doi.org/10.1016/S1357-2725(97)00094-0
  14. Liang, Y., Robinson, D.F., Dennig, J., Suske, G. and Fahl, W. E. (1996) Transcriptional regulation of the SIS/PDGF-B gene in human osteosarcoma cells by the Sp family of transcription factors. J. Biol. Chem. 271, 11792-11797. https://doi.org/10.1074/jbc.271.20.11792
  15. Lopes, J. E., Torgerson, T. R., Schubert, L. A., Anover, S. D., Ocheltree, E. L., Ochs, H. D. and Ziegler, S. F. (2006) Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor. J. Immunol. 177, 3133-3142. https://doi.org/10.4049/jimmunol.177.5.3133
  16. Mackay, J. P. and Crossley, M. (1998) Zinc fingers are sticking together. Trends Biochem. Sci. 23, 1-4. https://doi.org/10.1016/S0968-0004(97)01168-7
  17. Melchior, F. (2000) SUMO--nonclassical ubiquitin. Annu. Rev. Cell Dev. Biol. 16, 591-626. https://doi.org/10.1146/annurev.cellbio.16.1.591
  18. Miller, J., Mclachlan, A. D. and Klug, A. (1985) Repetitive zincbinding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 4, 1609-1614.
  19. Muller, S., Berger, M., Lehembre, F., Seeler, J. S., Haupt, Y. and Dejean, A. (2000) c-Jun and p53 activity is modulated by SUMO-1 modification. J. Biol. Chem. 275, 13321-13329. https://doi.org/10.1074/jbc.275.18.13321
  20. Noti, J. D. (1997) Sp3 mediates transcriptional activation of the leukocyte integrin genes CD11C and CD11B and cooperates with c-Jun to activate CD11C. J. Biol. Chem. 272, 24038-24045. https://doi.org/10.1074/jbc.272.38.24038
  21. Numoto, M., Niwa, O., Kaplan, J., Wong, K. K., Merrell, K., Kamiya, K., Yanagihara, K. and Calame, K. (1993) Transcriptional repressor ZF5 identifies a new conserved domain in zinc finger proteins. Nucleic Acids Res. 21, 3767-3775. https://doi.org/10.1093/nar/21.16.3767
  22. Poukka, H., Aarnisalo, P., Karvonen, U., Palvimo, J. J. and Janne, O. A. (1999) Ubc9 interacts with the androgen receptor and activates receptor-dependent transcription. J. Biol. Chem. 274, 19441-19446. https://doi.org/10.1074/jbc.274.27.19441
  23. Poukka, H., Karvonen, U., Janne, O. A. and Palvimo, J. J. (2000) Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1). Proc. Natl. Acad. Sci. USA 97, 14145-14150. https://doi.org/10.1073/pnas.97.26.14145
  24. Rodriguez, M. S., Dargemont, C. and Hay, R. T. (2001) SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting. J. Biol. Chem. 276, 12654-12659. https://doi.org/10.1074/jbc.M009476200
  25. Rodriguez, M. S., Desterro, J. M., Lain, S., Midgley, C. A., Lane, D. P. and Hay, R. T. (1999) SUMO-1 modification activates the transcriptional response of p53. EMBO J. 18, 6455-6461. https://doi.org/10.1093/emboj/18.22.6455
  26. Ross, S., Best, J. L., Zon, L. I. and Gill, G. (2002) SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization. Mol. Cell 10, 831-842. https://doi.org/10.1016/S1097-2765(02)00682-2
  27. Schoenherr, C. J. and Anderson, D. J. (1995) Silencing is golden: negative regulation in the control of neuronal gene transcription. Curr. Opin. Neurobiol. 5, 566-571. https://doi.org/10.1016/0959-4388(95)80060-3
  28. Shastry, B. S. (1996) Transcription factor IIIA (TFIIIA) in the second decade. J. Cell Sci. 109, 535-539.
  29. Suske, G. (1999) The Sp-family of transcription factors. Gene 238, 291-300. https://doi.org/10.1016/S0378-1119(99)00357-1
  30. Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A. and et al. (2001) The Sequence of the Human Genome. Science 291, 1304-1351. https://doi.org/10.1126/science.1058040
  31. Williams, A. J., Blacklow, S. C. and Collins, T. (1999) The zinc finger-associated SCAN box is a conserved oligomerization domain. Mol. Cell. Biol. 19, 8526-8535. https://doi.org/10.1128/MCB.19.12.8526
  32. Wolfe, S. A., Nekludova, L. and Pabo, C. O. (2000) DNA recognition by Cys2His2 zinc finger proteins. Annu. Rev. Biophys. Biomol. Struct. 29, 183-212. https://doi.org/10.1146/annurev.biophys.29.1.183
  33. Wu, Y., Yu, L., Bi, G., Luo, K., Zhou, G. and Zhao, S. (2003) Identification and characterization of two novel human SCAN domain-containing zinc finger genes ZNF396 and ZNF397. Gene 310, 193-201. https://doi.org/10.1016/S0378-1119(03)00551-1
  34. Zollman, S., Godt, D., Prive, G. G.., Couderc, J. L. and Laski, F. A. (1994) The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila. Proc. Natl. Acad. Sci. USA 91, 10717-10721. https://doi.org/10.1073/pnas.91.22.10717

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