| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print November 18, 2003
Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH 45267-0056
Corresponding Author: Alvaro.Puga{at}UC.EDU
Co-contamination with complex mixtures of carcinogenic metals, such as chromium, and polycyclic aromatic hydrocarbons is a common environmental problem with multiple biological consequences. Chromium exposure alters inducible gene expression, forms chromium-DNA adducts and chromium-DNA cross-links, and disrupts transcriptional activator/coactivator complexes. We have previously shown that exposure of mouse hepatoma Hepa-1 cells to chromate inhibits the induction of the Cyp1a1 and Nqo1 genes by dioxin. Here, we have teste the hypothesis that chromium blocks gene expression by interfering with the assembly of productive transcriptional complexes at the promoter of inducible genes. To this end, we have studied the effects of chromium on the expression of genes induced by B[a]P, another AHR agonist, and characterized the disruption of Cyp1a1 transcriptional induction by chromium. Gene expression profiling using high density microarray analysis revealed that the inhibitory effect of chromium on B[a]P-dependent gene induction was generalized, affecting the induction of over 50 different genes involved in a variety of signaling transduction pathways. The inhibitory effect of chromium on Cyp1a1 transcription was found to depend on the presence of promoter-proximal sequences and not on the cis-acting enhancer sequences that bind the AHT/ARNT complex. Using transient reporter assays and ChIP analyses, we found that chromium prevented the B[a]P-dependent release of HDAC-1 from Cyp1a1 chromatin and blocked p300 recruitment. These results provide a mechanistic explanation for the observation that chromium inhibits inducible, but not constitutive gene expression.
J. Biol. Chem, 10.1074/jbc.M310800200
Submitted on October 1, 2003
Revised on November 11, 2003
Accepted on November 18, 2003
Chromium inhibits transcription from PAH-inducible promoters by blocking the release of HDAC and preventing the binding of p300 to chromatin
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. C. M. Staal, D. S. Pushparajah, M. H. M. van Herwijnen, R. W. H. Gottschalk, L. M. Maas, C. Ioannides, F. J. van Schooten, and J. H. M. van Delft Interactions between polycyclic aromatic hydrocarbons in binary mixtures: Effects on gene expression and DNA adduct formation in precision-cut rat liver slices Mutagenesis, August 18, 2008; (2008) gen041v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schnekenburger, G. Talaska, and A. Puga Chromium Cross-Links Histone Deacetylase 1-DNA Methyltransferase 1 Complexes to Chromatin, Inhibiting Histone-Remodeling Marks Critical for Transcriptional Activation Mol. Cell. Biol., October 15, 2007; 27(20): 7089 - 7101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Suzuki and K. Nohara Regulatory Factors Involved in Species-specific Modulation of Arylhydrocarbon Receptor (AhR)-dependent Gene Expression in Humans and Mice J. Biochem., October 1, 2007; 142(4): 443 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chang, Y. Fan, S. Karyala, S. Schwemberger, C. R. Tomlinson, M. A. Sartor, and A. Puga Ligand-Independent Regulation of Transforming Growth Factor {beta}1 Expression and Cell Cycle Progression by the Aryl Hydrocarbon Receptor Mol. Cell. Biol., September 1, 2007; 27(17): 6127 - 6139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Reynolds, L. Stoddard, I. Bespalov, and A. Zhitkovich Ascorbate acts as a highly potent inducer of chromate mutagenesis and clastogenesis: linkage to DNA breaks in G2 phase by mismatch repair Nucleic Acids Res., January 28, 2007; 35(2): 465 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Matthews, B. Wihlen, J. Thomsen, and J.-A. Gustafsson Aryl Hydrocarbon Receptor-Mediated Transcription: Ligand-Dependent Recruitment of Estrogen Receptor {alpha} to 2,3,7,8-Tetrachlorodibenzo- p-Dioxin-Responsive Promoters Mol. Cell. Biol., July 1, 2005; 25(13): 5317 - 5328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Bonzo, S. Chen, A. Galijatovic, and R. H. Tukey Arsenite Inhibition of CYP1A1 Induction by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Independent of Cell Cycle Arrest Mol. Pharmacol., April 1, 2005; 67(4): 1247 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Moggs and G. Orphanides The Role of Chromatin in Molecular Mechanisms of Toxicity Toxicol. Sci., August 1, 2004; 80(2): 218 - 224. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
