Browse > Article
http://dx.doi.org/10.5352/JLS.2005.15.6.994

Transcriptional Activation and Repression of Cell Cycle Regulatory Molecules by Trichostatin A  

Baek Jong-Soo (Department of Dentistry, College of Medicine, Yeungnam University)
Lee Hee-Kyung (Department of Dentistry, College of Medicine, Yeungnam University)
Cho Young-Su (Department of Biotechnolory, College of Natural Resources and Life Science)
Kim Sung-Young (Department of Food Science, Andong Science College)
Park Kwan-Kyu (Department of Pathology, Catholic University of Daegu School of Medicine)
Chang Young-Chae (Department of Pathology, Catholic University of Daegu School of Medicine)
Publication Information
Journal of Life Science / v.15, no.6, 2005 , pp. 994-1004 More about this Journal
Abstract
The dihydrofolate reductase (dhfr) promoter contains cis-acting element for the transcription factors Spl and E2F. Transcription of dhfr gene shows maximal activity during the Gl/S phase of cell cycle. The member of the Spl transcriptional factor family can act as both negative and positive regulators of gene expression. There was a report that Spl-Rb and E2F4-pl30 complexes cooperate to establish stable repression of dhfr gene expression in CHOC400 cells. Here, we examined the role of HDAC in dhfr, cyclin E, and cyclin A gene regulation using the histone deacetylation inhibitor, trichostatin A (TSA) in U2OS and C33A cells, a Rb-positive human osteosarcoma cell line, and a Rb-negative cervical carcinoma cell line, respectively. When the dhfr promoter constructs were applied in U2OS cells, TSA markedly stimulated over 14-fold of dhfr promoter activity through dhfr-Spl sites by the deletion of an E2F element. In contrast, the deletion of dhfr-Spl binding sites completely abolished promoter stimulation by TSA. The dhfr promoter activity including dhfr-Spl sites increased only 2-fold in C33A cells. Promoter activity containing only dhfr-E2F site did not have much effect by the treatment of TSA in both U2OS and C33A cells. On the other hand, treatment with TSA induced significantly mRNA expression of dhfr and cyclin E, whereas levels of cyclin A decreased in U2OS cells, but had no effect in C33A cells. These results indicate that TSA have contradictory effect, activation of dhfr and cyclin E genes on Gl phase, and down-regulation of cyclin A on G2 phase through transcriptional regulation in U2OS cells.
Keywords
Trichostatin A; Spl; E2F; Osteosarcoma; Cervical dhfr;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Blake, M. C., Jambou, R. C., Swick, A. G., Kahn, J. W. and Azizkhan, J. C. 1990. Transcriptional initiation is controlled by upstream GC-box interactions in a TATA-less promoter. Mol. Cell. Biol. 10(12), 6632-6641
2 Eickhoff, B., Ruller, S., Laue, T., Kohler, G., Stahl, C., Schlaak, M. and van der Bosch, J. 2000. Trichostatin A modulates expression of p21waf1/cip1, Bcl-xL, ID1, ID2, ID3, CRAB2, GATA-2, hsp86 and TFIID/TAFII31 mRNA in human lung adenocarcinoma cells. Biol. Chem 381(2), 107-112   DOI   ScienceOn
3 Yoshida, M., Furumai, R., Nishiyama, M., Komatsu, Y., Nishino, N. and Horinouchi, S. 2001. Histone deacetylase as a new target for cancer chemotherapy. Cancer Chemother. Pharmacol. 48(Suppl 1), 20-26   DOI   ScienceOn
4 Zhang, H. S., Gavin, M., Dahiya, A., Postigo, A. A., Ma, D., Luo, R. X., Harbour, J. W. and Dean, D. C. 2000. Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF. Cell 101(1), 79-89   DOI   ScienceOn
5 Wade, M., Kowalik, T. F., Mudryj, M., Huang, E. S. and Azizkhan, J. C. 1992. E2F mediates dihydrofolate reductase promoter activation and multiprotein complex formation in human cytomegalovirus infection. Mol. Cell. Biol. 12(10), 4364-4374
6 Noe, V., Chen, C., Alemany, C., Nicolas, M., Caragol, I., Chasin, L. A. and Ciudad, C. J. 1997. Cell-growth regulation of the hamster dihydrofolate reductase gene promoter by transcription factor Sp1. Eur. J. Biochem. 249(1), 13-20   DOI   ScienceOn
7 Saito, A., Yamashita, T., Mariko, Y., Nosaka, Y., Tsuchiya, K., Ando, T., Suzuki, T., Tsuruo, T. and Nakanishi, O. 1999. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc. Natl. Acad. Sci. 96(8), 4592-4597
8 Santiago, C., Collins, M. and Johnson, L. F. 1984. In vitro and in vivo analysis of the control of dihydrofolate reductase gene transcription in serum-stimulated mouse fibroblasts. J. Cell. Physiol. 118(1), 79-86   DOI
9 Slansky, J. E., Li, Y., Kaelin, W. G. and Farnham, P. J. 1993. A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter. Mol. Cell. Biol. 13(3), 1610-1618
10 Vigushin, D. M. and Coombes, R. C. 2002. Histone deacetylase inhibitors in cancer treatment. Anticancer Drugs 13(1), 1-13   DOI   ScienceOn
11 Wade, P. A., Pruss, D. and Wolffe, A. P. 1997. Histone acetylation: chromatin in action. Trends Biochem. Sci. 22(4), 128-132   DOI   ScienceOn
12 Kao, H. Y., Ordentlich, P., Koyano-Nakagawa, N., Tang, Z., Downes, M., Kintner, C. R., Evans, R. M. and Kadesch, T. 1998. A histone deacetylase corepressor complex regulates the Notch signal transductionpathway. Genes Dev. 12(15), 2269-2277   DOI   ScienceOn
13 Wells, J. M., Illenye, S., Magae, J., Wu, C. L. and Heintz, N. H. 1997. Accumulation of E2F-4.DP-1 DNA binding complexes correlates with induction of dhfr gene expression during the G1 to S phase transition. J. Biol. Chem. 272(7), 4483-4492   DOI   ScienceOn
14 Wells, J., Held, P., Illenye, S. and Heintz, N. H. 1996. Protein-DNA interactions at the major and minor promoters of the divergently transcribed dhfr and rep3 genes during the Chinese hamster ovary cell cycle. Mol. Cell. Biol. 16(2), 634-647
15 Won, J., Yim, J. and Kim, T. K. 2002. Opposing regulatory roles of E2F in human telomerase reverse transcriptase (hTERT) gene expression in human tumour and normal somatic cells. FASEB J. 16, 1943-1945
16 Laherty, C. D., Yang, W. M., Sun, J. M., Davie, J. R., Seto, E., Eisenman, R. N. 1997. Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell 89(3), 349-356   DOI   ScienceOn
17 Marks, P. A., Richon, V. M., Breslow, R. and Rifkind, R. A. 2001. Histone deacetylase inhibitors as new cancer drugs. Curr. Opin. Oncol. 13(6), 477-483   DOI   ScienceOn
18 Marks, P., Rifkind, R. A., Richon, V. M., Breslow, R., Miller, T. and Kelly, W. K. 2001. Histone deacetylases and cancer: causes and therapies. Nat. Rev. Cancer 1(3), 194-202   DOI   ScienceOn
19 Means, A. L., Slansky, J. E., McMahon, S. L., Knuth, M. W. and Farnham, P. J. 1992. The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter. Mol. Cell. Biol. 12(3). 1054-1063
20 Huang, L., Sowa, Y., Sakai, T. and Pardee, A. B. 2000. Activation of the p21WAF1/CIP1 promoter independent of p53 by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) through the Sp1 sites. Oncogene 19(50), 5712-5719   DOI   ScienceOn
21 Farnham, P. J. and Schimke, R. T. 1986. Murine dihydrofolate reductase transcripts through the cell cycle. Mol. Cell. Biol. 6(2), 365-371
22 Murata, Y., Kim, H. G., Rogers, K. T., Udvadia, A. J. and Horowitz, J. M. 1994. Negative regulation of Sp1 trans-activation is correlated with the binding ofcellular proteins to theamino terminus of the Sp1 trans-activation domain. J. Biol. Chem. 269(32), 20674-20681
23 Nakano, K., Mizuno, T., Sowa, Y., Orita, T., Yoshino, T., Okuyama, Y., Fujita, T., Ohtani-Fujita, N., Matsukawa, Y., Tokino,T., Yamagishi, H., Oka, T., Nomura, H. and Sakai, T. 1997. Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line. J. Biol. Chem. 272(35), 22199-22206   DOI   ScienceOn
24 Ng, H. H. and Bird, A. 1999. DNA methylation and chromatin modification. Curr. Opin. Genet. Dev. 9(2), 158-163   DOI   ScienceOn
25 Ferrara, F. F., Fazi, F., Bianchini, A., Padula, F., Gelmetti, V., Minucci, S., Mancini, M., Pelicci, P. G., Lo Coco, F. and Nervi, C. 2001. Histone deacetylase-targeted treatment restores retinoic acid signaling and differentiation in acute myeloid leukemia. Cancer Res. 61(1), 2-7
26 Finnin, M. S., Donigian, J. R., Cohen, A., Richon, V. M., Rifkind, R. A., Marks, P. A. and Breslow Rand Pavletich, N. P. 1999. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 401, 188-193   DOI   ScienceOn
27 Han, J. W., Ahn, S. H., Kim, Y. K., Bae, G. U., Yoon, J. W., Hong, S., Lee, H. Y., Lee, Y. W. and Lee, H. W. 2001. Activation of p21(WAF1/Cip1) transcription through Sp1 sites by histone deacetylase inhibitor apicidin: involvement of protein kinaseC. J. Biol. Chem 276(45), 42084-42090   DOI   ScienceOn
28 Jensen, D. E., Black, A. R., Swick, A.G. and Azizkhan, J. C. 1997. Distinct roles for Sp1 and E2F sites in the growth/cell cycle regulation of the DHFR promoter. J. Cell. Biochem 67(1), 24-31   DOI   ScienceOn
29 Heinzel, T., Lavinsky, R. M., Mullen, T. M., Soderstrom, M., Laherty, C. D., Torchia, J., Yang, W. M., Brard, G., Ngo, S. D., Davie, J. R., Seto, E., Eisenman, R. N., Rose, D. W., Glass, C. K. and Rosenfeld, M. G. 1997. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature 387(6628), 43-48   DOI   ScienceOn
30 Hendrickson, S. L., Wu, J. S. and Johnson, L. F. 1980. Cell cycle regulation of dihydrofolate reductase mRNA metabolism in mouse fibroblasts. Proc. Natl. Acad. Sci. 77(9), 5140-5144
31 Johnson, L. F., Fuhrman, C. L. and Wiedemann, L. M. 1978. Regulation of dihydrofolate reductase gene expression in mouse fibroblasts during the transition from the resting to growing state. J. Cell. Physiol 97(Suppl 1), 397-306   DOI
32 Black, A. R., Jensen, D., Lin, S. Y. and Azizkhan, J. C. 1999. Growth/cell cycle regulation of Sp1 phosphorylation. J. Biol. Chem 274(3), 1207-1215   DOI   ScienceOn
33 Blake, M. C. and Azizkhan, J. C. 1989. Transcription factor E2F is required for efficient expression of the hamster dihydrofolate reductase gene in vitro and in vivo. Mol. Cell. Biol. 9(11), 4994-5002
34 Brehm, A., Miska, E. A., McCance, D. J., Reid, J. L., Bannister, A. J. and Kouzarides, T. 1998. Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391 (6667), 597-601   DOI   ScienceOn
35 Doetzlhofer, A., Rotheneder, H., Lagger, G., Koranda, M., Kurtev, V., Brosch, G., Wintersberger, E. and Seiser, C. 1999. Histone deacetylase 1 can repress transcription by binding to Sp1. Mol. Cell. Biol. 19, 5504-5511
36 Chang, Y. C., Illenye, S. and Heintz, N. H. 2001. Cooperation of E2F-p130 and Sp1-pRb complexes in repression of the Chinese hamster dhfr gene. Mol. Cell. Biol. 21(4), 1121-1131   DOI   ScienceOn
37 Ciudad, C. J., Morris, A. E., Jeng, C. and Chasin, L. A. 1992. Point mutational analysis of the hamster dihydrofolate reductase minimum promoter. J. Biol. Chem. 267(6), 3650-3656
38 DeCaprio, J. A., Ludlow, J. W., Lynch, D., Furukawa, Y., Griffin, J., Piwnica-Worms, H., Huang, C. M. and Livingston, D. M. 1989. The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell 58(6), 1085-109   DOI   ScienceOn
39 Farnham, P. J. and Schimke, R. T. 1985. Transcriptional regulation of mouse dihydrofolate reductase in the cell cycle. J. Biol. Chem 260(12), 7675-7680
40 Johnstone, R. W. 2002. Histone-deacetylase inhibitors. Nat. Rev. Drug Discov. 1(4), 287-299   DOI   ScienceOn
41 Sowa, Y., Orita, T., Minamikawa, S., Nakano, K., Mizuno, T., Nomura, H. and Sakai, T. 1997. Histone deacetylase inhibitor activates the WAF1/Cip1 gene promoter through the Sp1 sites. Biochem. Biophys. Res. Commun. 241(1), 142-150   DOI   ScienceOn
42 Vigushin, D. M., Ali, S., Pace, P. E., Mirsaidi, N., Ito, K., Adcock, I. and Coombes, R. C. 2001. Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo. Clin. Cancer Res. 7(4), 971-976