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Yin-Yang 1 and Yin-Yang 2 exert opposing effects on the promoter activity of interleukin 4

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Abstract

Interleukin (IL)-4 acts on T cells as a growth and activation factor, and promotes the differentiation of type 2 T helper cells. In T cells, expression of the gene encoding IL-4 is regulated by inducible or constitutive factors. Yin-Yang (YY)-1 is one of constitutive transcription factors binding to the IL-4 promoter. The recently identified YY2 protein is similar to YY1, with both sharing high levels of homology in their zinc finger motifs. However, the role of YY2 in T cells is unclear. YY1 and YY2 were constitutively expressed in EL4 T cells, and their expression was not dependent on stimulation. IL-4 promoter (−741/+56 fragment) activity was enhanced by YY1, but inhibited by YY2. The enhanced IL-4 promoter activity by YY1 was reduced by simultaneous expression of YY2. In addition, the DNA binding affinity of YY1 to the IL-4 promoter was adversely affected by YY2. Our results suggest that YY1 and YY2 exert opposing effects on the IL-4 promoter as they compete for the same DNA binding sites.

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References

  • Atchison, L., A. Ghias, F. Wilkinson, N. Bonini, and M.L. Atchison. 2003. Transcription factor YY1 functions as a PcG protein in vivo. EMBO Journal 22: 1347–1358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Austen, M., B. Luscher, and J.M. Luscher-Firzlaff. 1997. Characterization of the transcriptional regulator YY1. The bipartite transactivation domain is independent of interaction with the TATA box-binding protein, transcription factor IIB, TAFII55, or cAMP-responsive element-binding protein (CPB)-binding protein. Journal of Biological Chemistry 272: 1709–1717.

    Article  CAS  PubMed  Google Scholar 

  • Barbulescu, K., C. Becker, J.F. Schlaak, E. Schmitt, K.H.M.Z. Buschenfelde, and M.F. Neurath. 1998. IL-12 and IL-18 differentially regulate the transcriptional activity of the human IFN-gamma promoter in primary CD4+T lymphocytes. The Journal of Immunology 160: 3642–3647.

    CAS  PubMed  Google Scholar 

  • Brown, M.A., and J. Hural. 1997. Functions of IL-4 and control of its expression. Critical Reviews in Immunology 17: 1–32.

    Article  CAS  PubMed  Google Scholar 

  • Brown, J.L., D. Mucci, M. Whiteley, M.L. Dirksen, and J.A. Kassis. 1998. The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1. Molecular Cell 1: 1057–1064.

    Article  CAS  PubMed  Google Scholar 

  • Brusselle, G.G., J.C. Kips, J.H. Tavernier, J.G. Van Der Heyden, C.A. Cuvelier, R.A. Pauwels, and H. Bluethmann. 1994. Attenuation of allergic airway inflammation in IL-4 deficient mice. Clinical and Experimental Allergy 24: 73–80.

    Article  CAS  PubMed  Google Scholar 

  • Chung, S.W., B.Y. Kang, and T.S. Kim. 2003. Inhibition of interleukin-4 production in CD4+T cells by peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands: involvement of physical association between PPAR-gamma and the nuclear factor of activated T cells transcription factor. Molecular Pharmacology 64: 1169–1179.

    Article  CAS  PubMed  Google Scholar 

  • Donohoe, M.E., X. Zhang, L. Mcginnis, J. Biggers, E. Li, and Y. Shi. 1999. Targeted disruption of mouse Yin Yang 1 transcription factor results in peri-implantation lethality. Molecular and Cellular Biology 19: 7237–7244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galvin, K.M., and Y. Shi. 1997. Multiple mechanisms of transcriptional repression by YY1. Molecular and Cellular Biology 17: 3723–3732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gordon, S.J., S. Saleque, and B.K. Birshtein. 2003. Yin Yang 1 is a lipopolysaccharide-inducible activator of the murine 3′ Igh enhancer, hs3. The Journal of Immunology 170: 5549–5557.

    Article  CAS  PubMed  Google Scholar 

  • Gordon, S., G. Akopyan, H. Garban, and B. Bonavida. 2006. Transcription factor YY1: structure, function, and therapeutic implications in cancer biology. Oncogene 25: 1125–1142.

    Article  CAS  PubMed  Google Scholar 

  • Gronroos, E., A.A. Terentiev, T. Punga, and J. Ericsson. 2004. YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress. Proceedings of the National Academy of Sciences USA 101: 12165–12170.

    Article  Google Scholar 

  • Guo, J., V. Casolaro, E. Seto, W.M. Yang, C. Chang, M.C. Seminario, J. Keen, and S.N. Georas. 2001. Yin-Yang 1 activates interleukin-4 gene expression in T cells. Journal of Biological Chemistry 276: 48871–48878.

    Article  CAS  PubMed  Google Scholar 

  • Guo, J., X. Lin, M.A. Williams, Q. Hamid, and S.N. Georas. 2008. Yin-Yang 1 regulates effector cytokine gene expression and T(H)2 immune responses. Journal of Allergy and Clinical Immunology 122: 195–201.

    Article  CAS  PubMed  Google Scholar 

  • He, Y., J. Dupree, J. Wang, J. Sandoval, J. Li, H. Liu, Y. Shi, K.A. Nave, and P. Casaccia-Bonnefil. 2007. The transcription factor Yin Yang 1 is essential for oligodendrocyte progenitor differentiation. Neuron 55: 217–230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hiromura, M., C.H. Choi, N.A. Sabourin, H. Jones, D. Bachvarov, and A. Usheva. 2003. YY1 is regulated by O-linked N-acetylglucosaminylation (O-glcNAcylation). Journal of Biological Chemistry 278: 14046–14052.

    Article  CAS  PubMed  Google Scholar 

  • Ho, I.C., M.R. Hodge, J.W. Rooney, and L.H. Glimcher. 1996. The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 85: 973–983.

    Article  CAS  PubMed  Google Scholar 

  • Hwang, S.S., Y.U. Kim, S. Lee, S.W. Jang, M.K. Kim, B.H. Koh, W. Lee, J. Kim, A. Souabni, M. Busslinger, and G.R. Lee. 2013. Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation. Proceedings of the National Academy of Sciences USA 110: 276–281.

    Article  CAS  Google Scholar 

  • Kaplan, M.H., U. Schindler, S.T. Smiley, and M.J. Grusby. 1996. Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4: 313–319.

    Article  CAS  PubMed  Google Scholar 

  • Kiani, A., F.J. Garcia-Cozar, I. Habermann, S. Laforsch, T. Aebischer, G. Ehninger, and A. Rao. 2001. Regulation of interferon-gamma gene expression by nuclear factor of activated T cells. Blood 98: 1480–1488.

    Article  CAS  PubMed  Google Scholar 

  • Kim, J.D., C. Faulk, and J. Kim. 2007. Retroposition and evolution of the DNA-binding motifs of YY1, YY2 and REX1. Nucleic Acids Research 35: 3442–3452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mordvinov, V.A., G.T. Schwenger, R. Fournier, M.L. De Boer, S.E. Peroni, A.D. Singh, S. Karlen, J.W. Holland, and C.J. Sanderson. 1999. Binding of YY1 and Oct1 to a novel element that downregulates expression of IL-5 in human T cells. Journal of Allergy and Clinical Immunology 103: 1125–1135.

    Article  CAS  PubMed  Google Scholar 

  • Mosmann, T.R., and R.L. Coffman. 1989. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology 7: 145–173.

    Article  CAS  PubMed  Google Scholar 

  • Mosmann, T.R., H. Cherwinski, M.W. Bond, M.A. Giedlin, and R.L. Coffman. 1986. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. The Journal of Immunology 136: 2348–2357.

    CAS  PubMed  Google Scholar 

  • Nguyen, N., X. Zhang, N. Olashaw, and E. Seto. 2004. Molecular cloning and functional characterization of the transcription factor YY2. Journal of Biological Chemistry 279: 25927–25934.

    Article  CAS  PubMed  Google Scholar 

  • Oei, S.L., and Y. Shi. 2001. Poly(ADP-ribosyl)ation of transcription factor Yin Yang 1 under conditions of DNA damage. Biochemical and Biophysical Research Communications 285: 27–31.

    Article  CAS  PubMed  Google Scholar 

  • Parronchi, P., D. Macchia, M.P. Piccinni, P. Biswas, C. Simonelli, E. Maggi, M. Ricci, A.A. Ansari, and S. Romagnani. 1991. Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. Proceedings of the National Academy of Sciences USA 88: 4538–4542.

    Article  CAS  Google Scholar 

  • Parronchi, P., M. De Carli, R. Manetti, C. Simonelli, M.P. Piccinni, D. Macchia, E. Maggi, G. Del Prete, M. Ricci, and S. Romagnani. 1992. Aberrant interleukin (IL)-4 and IL-5 production in vitro by CD4+ helper T cells from atopic subjects. European Journal of Immunology 22: 1615–1620.

    Article  CAS  PubMed  Google Scholar 

  • Petkova, V., M.J. Romanowski, I. Sulijoadikusumo, D. Rohne, P. Kang, T. Shenk, and A. Usheva. 2001. Interaction between YY1 and the retinoblastoma protein. Regulation of cell cycle progression in differentiated cells. Journal of Biological Chemistry 276: 7932–7936.

    Article  CAS  PubMed  Google Scholar 

  • Pisaneschi, G., S. Ceccotti, M.L. Falchetti, S. Fiumicino, F. Carnevali, and E. Beccari. 1994. Characterization of FIII/YY1, a Xenopus laevis conserved zinc-finger protein binding to the first exon of L1 and L14 ribosomal protein genes. Biochemical and Biophysical Research Communications 205: 1236–1242.

    Article  CAS  PubMed  Google Scholar 

  • Ranger, A.M., M.R. Hodge, E.M. Gravallese, M. Oukka, L. Davidson, F.W. Alt, F.C. De La Brousse, T. Hoey, M. Grusby, and L.H. Glimcher. 1998. Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc. Immunity 8: 125–134.

    Article  CAS  PubMed  Google Scholar 

  • Rezai-Zadeh, N., X. Zhang, F. Namour, G. Fejer, Y.D. Wen, Y.L. Yao, I. Gyory, K. Wright, and E. Seto. 2003. Targeted recruitment of a histone H4-specific methyltransferase by the transcription factor YY1. Genes & Development 17: 1019–1029.

    Article  CAS  Google Scholar 

  • Seto, E., B. Lewis, and T. Shenk. 1993. Interaction between transcription factors Sp1 and YY1. Nature 365: 462–464.

    Article  CAS  PubMed  Google Scholar 

  • Shi, Y., E. Seto, L.S. Chang, and T. Shenk. 1991. Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell 67: 377–388.

    Article  CAS  PubMed  Google Scholar 

  • Shi, Y., J.S. Lee, and K.M. Galvin. 1997. Everything you have ever wanted to know about Yin Yang 1. Biochimica et Biophysica Acta 1332: F49–F66.

    CAS  PubMed  Google Scholar 

  • Shrivastava, A., S. Saleque, G.V. Kalpana, S. Artandi, S.P. Goff, and K. Calame. 1993. Inhibition of transcriptional regulator Yin-Yang-1 by association with c-Myc. Science 262: 1889–1892.

    Article  CAS  PubMed  Google Scholar 

  • Sokol, C.L., G.M. Barton, A.G. Farr, and R. Medzhitov. 2008. A mechanism for the initiation of allergen-induced T helper type 2 responses. Nature Immunology 9: 310–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song, Z., V. Casolaro, R. Chen, S.N. Georas, D. Monos, and S.J. Ono. 1996. Polymorphic nucleotides within the human IL-4 promoter that mediate overexpression of the gene. The Journal of Immunology 156: 424–429.

    CAS  PubMed  Google Scholar 

  • Swain, S.L. 1993. IL4 dictates T-cell differentiation. Research in Immunology 144: 616–620.

    Article  CAS  PubMed  Google Scholar 

  • Sweetser, M.T., T. Hoey, Y.L. Sun, W.M. Weaver, G.A. Price, and C.B. Wilson. 1998. The roles of nuclear factor of activated T cells and ying-yang 1 in activation-induced expression of the interferon-gamma promoter in T cells. Journal of Biological Chemistry 273: 34775–34783.

    Article  CAS  PubMed  Google Scholar 

  • Thomas, M.J., and E. Seto. 1999. Unlocking the mechanisms of transcription factor YY1: are chromatin modifying enzymes the key? Gene 236: 197–208.

    Article  CAS  PubMed  Google Scholar 

  • Wang, J., M.F. Shannon, and I.G. Young. 2006. A role for Ets1, synergizing with AP-1 and GATA-3 in the regulation of IL-5 transcription in mouse Th2 lymphocytes. International Immunology 18: 313–323.

    Article  CAS  PubMed  Google Scholar 

  • Wang, X., Y. Feng, L. Xu, Y. Chen, Y. Zhang, D. Su, G. Ren, J. Lu, and B. Huang. 2008. YY1 restrained cell senescence through repressing the transcription of p16. Biochimica et Biophysica Acta 1783: 1876–1883.

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson, F.H., K. Park, and M.L. Atchison. 2006. Polycomb recruitment to DNA in vivo by the YY1 REPO domain. Proceedings of the National Academy of Sciences USA 103: 19296–19301.

    Article  CAS  Google Scholar 

  • Yant, S.R., W. Zhu, D. Millinoff, J.L. Slightom, M. Goodman, and D.L. Gumucio. 1995. High affinity YY1 binding motifs: identification of two core types (ACAT and CCAT) and distribution of potential binding sites within the human beta globin cluster. Nucleic Acids Research 23: 4353–4362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao, Y.L., W.M. Yang, and E. Seto. 2001. Regulation of transcription factor YY1 by acetylation and deacetylation. Molecular and Cellular Biology 21: 5979–5991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye, J., M. Cippitelli, L. Dorman, J.R. Ortaldo, and H.A. Young. 1996. The nuclear factor YY1 suppresses the human gamma interferon promoter through two mechanisms: inhibition of AP1 binding and activation of a silencer element. Molecular and Cellular Biology 16: 4744–4753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, D.H., L. Cohn, P. Ray, K. Bottomly, and A. Ray. 1997. Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. Journal of Biological Chemistry 272: 21597–21603.

    Article  CAS  PubMed  Google Scholar 

  • Zhou, Q., R.W. Gedrich, and D.A. Engel. 1995. Transcriptional repression of the c-fos gene by YY1 is mediated by a direct interaction with ATF/CREB. Journal of Virology 69: 4323–4330.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0006261).

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Authors and Affiliations

  1. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea

    Sung Ho Lee, Hyung Min Jeong, Kwang Youl Lee & Bok Yun Kang

  2. College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea

    Young-Chang Cho

  3. Department of Food and Nutrition, Mokpo National University, Muan, Jeonnam, Republic of Korea

    Kyung Hee Kim

  4. College of Pharmacy, CHA University, Seongnam, Gyeonggi, Republic of Korea

    Hyun Jin Choi

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  1. Sung Ho Lee
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Correspondence to Kwang Youl Lee or Bok Yun Kang.

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Lee, S.H., Cho, YC., Jeong, H.M. et al. Yin-Yang 1 and Yin-Yang 2 exert opposing effects on the promoter activity of interleukin 4. Arch. Pharm. Res. 39, 547–554 (2016). https://doi.org/10.1007/s12272-015-0622-7

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