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Cellular and Molecular Biology Letters

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Volume 15, Issue 4

ZNF300, a recently identified human transcription factor, activates the human IL-2Rβ promoter through the overlapping ZNF300/EGR1 binding site

Lu Xue / Hongling Qiu / Jian Ma / Mingxiong Guo / Wenxin Li
Published Online: 2010-09-24 | DOI: https://doi.org/10.2478/s11658-010-0025-1


ZNF300 was recently identified as a member of the human KRAB/C2H2 zinc finger protein family. Little is known about the role of ZNF300 in human gene regulation networks. In this study, the DNA-binding property of ZNF300 was further analyzed. We found that the recombinant ZNF300 could bind to the binding site 5′-GCGGGGGCG-3′ of Egr1, another member of the KRAB/C2H2 zinc finger protein family. Similarly, recombinant Egr1 also showed a similar binding affinity to the ZNF300 binding site 5′-CTGGGGGCG-3′. Bioinformatics analysis revealed that there is an overlapping ZNF300/Egr1 binding site in the human IL-2Rβ promoter region, which was previously known to be recognized by endogenous Egr1. Electrophoretic mobility shift assays showed that endogenous ZNF300 could also bind to this site. A transient transfection assay revealed that both ZNF300 and Egr1 could transactivate the IL-2Rβ promoter, and that the activation was abrogated by a mutation of residues in the overlapping ZNF300/Egr1 binding site. Co-expression of ZNF300 and Egr1 led to enhanced IL-2Rβ promoter activity. Thus, ZNF300 is likely to be another regulator of the human IL-2Rβ promoter.

Keywords: ZNF300; Egr-1; IL-2Rβ promoter; Activation

  • [1] Orphanides, G. and Reinberg, D. A unified theory of gene expression. Cell 108 (2002) 439–451. http://dx.doi.org/10.1016/S0092-8674(02)00655-4CrossrefGoogle Scholar

  • [2] Brandenberger, R., Wei, H., Zhang, S., Lei, S., Murage, J., Fisk, G.J., Li, Y., Xu, C., Fang, R., Guegler, K., Rao, M.S., Mandalam, R., Lebkowski, J. and Stanton, L.W. Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nat. Biotechnol. 22 (2004) 707–716. http://dx.doi.org/10.1038/nbt971CrossrefGoogle Scholar

  • [3] Schuh, R., Aicher, W., Gaul, U., Cote, S., Preiss, A., Maier, D., Seifert, E., Nauber, U., Schroder, C., Kemler, R. and Jäckle, H. A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Kruppel, a Drosophila segmentation gene. Cell 47 (1986) 1025–1032. http://dx.doi.org/10.1016/0092-8674(86)90817-2CrossrefGoogle Scholar

  • [4] Dai, K.S. and Liew, C.C. Chromosomal, in silico and in vitro expression analysis of cardiovascular-based genes encoding zinc finger proteins. J. Mol. Cell Cardiol. 31 (1999) 1749–1769. http://dx.doi.org/10.1006/jmcc.1999.1011CrossrefGoogle Scholar

  • [5] Decker, E.L., Nehmann, N., Kampen, E., Eibel, H., Zipfel, P.F. and Skerka, C. Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression. Nucleic Acids Res. 31 (2003) 911–921. http://dx.doi.org/10.1093/nar/gkg186CrossrefGoogle Scholar

  • [6] Gou, D., Wang, J., Gao, L., Sun, Y., Peng, X., Huang, J. and Li, W. Identification and functional analysis of a novel human KRAB/C2H2 zinc finger gene ZNF300. Biochim. Biophys. Acta. 1676 (2004) 203–209. Google Scholar

  • [7] Bowden, N.A., Croft, A. and Scott, R.J. Gene expression profiling in familial adenomatous polyposis adenomas and desmoid disease. Hered. Cancer Clin. Pract. 5 (2007) 79–96. http://dx.doi.org/10.1186/1897-4287-5-2-79CrossrefWeb of ScienceGoogle Scholar

  • [8] Ferguson, L.R., Philpott, M. and Dryland, P. Nutrigenomics in the whole-genome scanning era: Crohn’s disease as example. Cell. Mol. Life Sci. 64 (2007) 3105–3118. http://dx.doi.org/10.1007/s00018-007-7303-8CrossrefWeb of ScienceGoogle Scholar

  • [9] Church, D.M., Goodstadt, L., Hillier, L.W., Zody, M.C., Goldstein, S., She, X., Bult, C.J., Agarwala, R., Cherry, J.L., DiCuccio, M., Hlavina, W., Kapustin, Y., Meric, P., Maglott, D., Birtle, Z., Marques, A.C., Graves, T., Zhou, S., Teague, B., Potamousis, K., Churas, C., Place, M., Herschleb, J., Runnheim, R., Forrest, D., Amos-Landgraf, J., Schwartz, D.C., Cheng, Z., Lindblad-Toh, K., Eichler, E.E. and Ponting, C.P. Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 7 (2009) e1000112. http://dx.doi.org/10.1371/journal.pbio.1000112Web of ScienceCrossrefGoogle Scholar

  • [10] Qiu, H., Xue, L., Gao, L., Shao, H., Wang, D., Guo, M. and Li, W. Identification of the DNA binding element of the human ZNF300 protein. Cell. Mol. Biol. Lett. 13 (2008) 391–403. http://dx.doi.org/10.2478/s11658-008-0005-xCrossrefGoogle Scholar

  • [11] Bernstein, S.H., Kharbanda, S.M., Sherman, M.L., Sukhatme, V.P. and Kufe, D.W. Posttranscriptional regulation of the zinc finger-encoding EGR-1 gene by granulocyte-macrophage colony-stimulating factor in human U-937 monocytic leukemia cells: involvement of a pertussis toxin-sensitive G protein. Cell Growth Differ. 2 (1991) 273–278. Google Scholar

  • [12] Milbrandt, J. A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science 238 (1987) 797–799. http://dx.doi.org/10.1126/science.3672127CrossrefGoogle Scholar

  • [13] Seyfert, V.L., McMahon, S.B., Glenn, W.D., Yellen, A.J., Sukhatme, V.P., Cao, X.M. and Monroe, J.G. Methylation of an immediate-early inducible gene as a mechanism for B cell tolerance induction. Science 250 (1990) 797–800. http://dx.doi.org/10.1126/science.2237429CrossrefGoogle Scholar

  • [14] Suva, L.J., Ernst, M. and Rodan, G.A. Retinoic acid increases zif268 early gene expression in rat preosteoblastic cells. Mol. Cell Biol. 11 (1991) 2503–2510. Google Scholar

  • [15] Kim, J.C., Yoon, J.B., Koo, H.S. and Chung, I.K. Cloning and characterization of the 5′-flanking region for the human topoisomerase III gene. J. Biol. Chem. 273 (1998) 26130–26137. http://dx.doi.org/10.1074/jbc.273.40.26130CrossrefGoogle Scholar

  • [16] Lin, J.X. and Leonard, W.J. The immediate-early gene product Egr-1 regulates the human interleukin-2 receptor beta-chain promoter through noncanonical Egr and Sp1 binding sites. Mol. Cell Biol. 17 (1997) 3714–3722. Google Scholar

  • [17] Lin, J.X., Bhat, N.K., John, S., Queale, W.S. and Leonard, W.J. Characterization of the human interleukin-2 receptor beta-chain gene promoter: regulation of promoter activity by ets gene products. Mol. Cell Biol. 13 (1993) 6201–6210. Google Scholar

  • [18] Minc, E., de Coppet, P., Masson, P., Thiety, L., Dutertre, S., Amor-Gueret, M. and Jaulin, C. The human copper-zinc superoxide dismutase gene (SOD1) proximal promoter is regulated by Sp1, Egr-1, and WT1 via non-canonical binding sites. J. Biol. Chem. 274 (1999) 503–509. http://dx.doi.org/10.1074/jbc.274.1.503CrossrefGoogle Scholar

About the article

Published Online: 2010-09-24

Published in Print: 2010-12-01

Citation Information: Cellular and Molecular Biology Letters, Volume 15, Issue 4, Pages 530–540, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-010-0025-1.

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© 2010 University of Wrocław, Poland. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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