Nucleic Acids Research, 2003, Vol. 31, No. 6 1693-1703
© 2003 Oxford University Press
Histone deacetylase inhibitors stimulate mitochondrial HMG-CoA synthase gene expression via a promoter proximal Sp1 site
Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Av. Diagonal 643, 08028 Barcelona, Spain
*To whom correspondence should be addressed. Tel: +34 93 403 45 00; Fax: +34 93 402 18 96; Email: pmar{at}farmacia.far.ub.es
The expression of mitochondrial HMG-CoA synthase in the colon has been correlated with the levels of butyrate present in this tissue. We report here that the effect of butyrate on mitochondrial HMG-CoA synthase gene expression is exerted in vivo at the transcriptional level, and that trichostatin A (TSA), a specific histone deacetylase inhibitor, also induces transcriptional activity and mRNA expression of the gene in human cell lines derived from colon carcinoma. Using chromatin immunoprecipitation assays, we show that histone deacetylase 1 (HDAC1) is associated with the endogenous mitochondrial HMG-CoA synthase promoter and that TSA induction correlates with hyperacetylation of H4 histone associated with the 5' flanking region of the gene. Overexpression of HDAC1 activity leads consistently to mitochondrial HMG-CoA synthase promoter hypoacetylation and reduces its transcriptional activity. The effect of butyrate and TSA maps to a single Sp1 site present in the proximal promoter of the gene, which is able to bind Sp1 and Sp3 proteins. Interestingly, the binding affinity of Sp1 and Sp3 proteins to the Sp1 site correlates with the TSA responsiveness of the promoter. Using a one-hybrid system (GAL4-Sp1 and GAL4-Sp3), we show that both proteins can mediate responsiveness to TSA in CaCo-2 cells employing distinct mechanisms.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Yoshioka, H. Kamitani, T. Watanabe, and T. E. Eling Nonsteroidal Anti-inflammatory Drug-activated Gene (NAG-1/GDF15) Expression Is Increased by the Histone Deacetylase Inhibitor Trichostatin A J. Biol. Chem., November 28, 2008; 283(48): 33129 - 33137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, M. Liao, and M. L. Dufau Unlocking Repression of the Human Luteinizing Hormone Receptor Gene by Trichostatin A-induced Cell-specific Phosphatase Release J. Biol. Chem., August 29, 2008; 283(35): 24039 - 24046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Liu, A. E. L. Tee, A. Porro, S. A. Smith, T. Dwarte, P. Y. Liu, N. Iraci, E. Sekyere, M. Haber, M. D. Norris, et al. Activation of tissue transglutaminase transcription by histone deacetylase inhibition as a therapeutic approach for Myc oncogenesis PNAS, November 20, 2007; 104(47): 18682 - 18687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wu, X. Zhang, M. Salmon, and Z. E. Zehner The zinc finger repressor, ZBP-89, recruits histone deacetylase 1 to repress vimentin gene expression Genes Cells, August 1, 2007; 12(8): 905 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Md. R. Amin, P. K. Dudeja, K. Ramaswamy, and J. Malakooti Involvement of Sp1 and Sp3 in differential regulation of human NHE3 promoter activity by sodium butyrate and IFN-{gamma}/TNF-{alpha} Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G374 - G382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Kiela, N. Kuscuoglu, A. J. Midura, M. T. Midura-Kiela, C. B. Larmonier, M. Lipko, and F. K. Ghishan Molecular mechanism of rat NHE3 gene promoter regulation by sodium butyrate Am J Physiol Cell Physiol, July 1, 2007; 293(1): C64 - C74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhang, M. Liao, and M. L. Dufau Phosphatidylinositol 3-Kinase/Protein Kinase C{zeta}-Induced Phosphorylation of Sp1 and p107 Repressor Release Have a Critical Role in Histone Deacetylase Inhibitor-Mediated Depression of Transcription of the Luteinizing Hormone Receptor Gene. Mol. Cell. Biol., September 1, 2006; 26(18): 6748 - 6761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Camarero, C. Mascaro, C. Mayordomo, F. Vilardell, D. Haro, and P. F. Marrero Ketogenic HMGCS2 Is a c-Myc Target Gene Expressed in Differentiated Cells of Human Colonic Epithelium and Down-Regulated in Colon Cancer Mol. Cancer Res., September 1, 2006; 4(9): 645 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Uchida, T. Maruyama, T. Nagashima, H. Asada, and Y. Yoshimura Histone Deacetylase Inhibitors Induce Differentiation of Human Endometrial Adenocarcinoma Cells through Up-Regulation of Glycodelin Endocrinology, December 1, 2005; 146(12): 5365 - 5373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Puppin, F. D'Aurizio, A. V. D'Elia, L. Cesaratto, G. Tell, D. Russo, S. Filetti, E. Ferretti, E. Tosi, T. Mattei, et al. Effects of Histone Acetylation on Sodium Iodide Symporter Promoter and Expression of Thyroid-Specific Transcription Factors Endocrinology, September 1, 2005; 146(9): 3967 - 3974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-C. Huang and C.-C. Chen Akt Phosphorylation of p300 at Ser-1834 Is Essential for Its Histone Acetyltransferase and Transcriptional Activity Mol. Cell. Biol., August 1, 2005; 25(15): 6592 - 6602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Gan, Y. H. Shen, J. Wang, X. Wang, B. Utama, J. Wang, and X. L. Wang Role of Histone Deacetylation in Cell-specific Expression of Endothelial Nitric-oxide Synthase J. Biol. Chem., April 22, 2005; 280(16): 16467 - 16475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ye, D. Shedd, and G. Miller An Sp1 Response Element in the Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50 Promoter Mediates Lytic Cycle Induction by Butyrate J. Virol., February 1, 2005; 79(3): 1397 - 1408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Kim, J.-W. Park, J.-Y. Lee, and T. K. Kwon Sodium butyrate sensitizes TRAIL-mediated apoptosis by induction of transcription from the DR5 gene promoter through Sp1 sites in colon cancer cells Carcinogenesis, October 1, 2004; 25(10): 1813 - 1820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Pile, P. T. Spellman, R. J. Katzenberger, and D. A. Wassarman The SIN3 Deacetylase Complex Represses Genes Encoding Mitochondrial Proteins: IMPLICATIONS FOR THE REGULATION OF ENERGY METABOLISM J. Biol. Chem., September 26, 2003; 278(39): 37840 - 37848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ferguson, P. A. Henry, and R. A. Currie Histone deacetylase inhibition is associated with transcriptional repression of the Hmga2 gene Nucleic Acids Res., June 15, 2003; 31(12): 3123 - 3133. [Abstract] [Full Text] [PDF]
|
|