| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print August 14, 2000
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555
Corresponding Author: samitra{at}utmb.edu
O6 methylguanine-DNA methyltransferase (MGMT)1, a ubiquitous DNA repair protein, removes O6 alkylguanine from DNA, including cytotoxic O6 - chloroethylguanine induced by chemotherapeutic N- alkyl N-nitrosourea-type drugs, e.g., 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). Tumor cell resistance to BCNU could be often correlated to its MGMT level, which varies widely in different tumor cells. Treating the pancreatic carcinoma cell line MIA PaCa-2 with trichostatin A (TSA), a specific inhibitor of histone deacetylase, increased MGMT mRNA and protein levels by 2-3 fold. Surprisingly, TSA treatment increased MGMT promoter-dependent luciferase activity by some 40- fold in a transient reporter expression assay. Deletion and point mutation analysis showed that two AP-1 binding sites in the promoter are involved in promoter activation by TSA. Ectopic expression of the transcriptional coactivators CBP (CREB binding protein) and p300, which have intrinsic histone acetyltransferease (HAT) activity, enhanced luciferase expression. Overexpression of adenovirus E1A, which binds CBP/p300, strongly inhibited both basal and TSA-inducible MGMT promoter activity, while a mutant E1A, defective in binding CBP/p300, did not. Chromatin immunoprecipitation assays revealed that TSA treatment increased histone acetylation in the endogenous MGMT promoter region, which also showed association with CBP/p300. Taken together, our results suggest that targeted histone acetylation results in the remodeling of chromatin by recruitment of the coactivator CBP/p300 and constitute an important step in regulating MGMT expression.
J. Biol. Chem, 10.1074/jbc.M005447200
Submitted on June 21, 2000
Revised on August 8, 2000
Accepted on August 14, 2000
Regulation of the human O6-methylguanine-DNA methyltransferase (MGMT) gene by transcriptional coactivators CBP and p300
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. M. Alonso, C. Gomez-Manzano, B. N. Bekele, W.K. A. Yung, and J. Fueyo Adenovirus-Based Strategies Overcome Temozolomide Resistance by Silencing the O6-Methylguanine-DNA Methyltransferase Promoter Cancer Res., December 15, 2007; 67(24): 11499 - 11504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fontijn, A. D. Adema, K. K. Bhakat, H. M. Pinedo, G. J. Peters, and E. Boven O6-Methylguanine-DNA-methyltransferase promoter demethylation is involved in basic fibroblast growth factor induced resistance against temozolomide in human melanoma cells Mol. Cancer Ther., October 1, 2007; 6(10): 2807 - 2815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Alimirah, J. Chen, F. J. Davis, and D. Choubey IFI16 in Human Prostate Cancer Mol. Cancer Res., March 1, 2007; 5(3): 251 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Bhakat and S. Mitra CpG methylation-dependent repression of the human O6-methylguanine-DNA methyltransferase gene linked to chromatin structure alteration Carcinogenesis, August 1, 2003; 24(8): 1337 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, J. Wong, S. Y. Tsai, M.-J. Tsai, and B. W. O'Malley Progesterone and Glucocorticoid Receptors Recruit Distinct Coactivator Complexes and Promote Distinct Patterns of Local Chromatin Modification Mol. Cell. Biol., June 1, 2003; 23(11): 3763 - 3773. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Margison, A. C. Povey, B. Kaina, and M. F. Santibanez Koref Variability and regulation of O6-alkylguanine-DNA alkyltransferase Carcinogenesis, April 1, 2003; 24(4): 625 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sharma and J. D. Fondell Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo PNAS, June 11, 2002; 99(12): 7934 - 7939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ray, C. T. Sherman, M. Lu, and A. R. Brasier Angiotensinogen Gene Expression Is Dependent on Signal Transducer and Activator of Transcription 3-Mediated p300/cAMP Response Element Binding Protein-Binding Protein Coactivator Recruitment and Histone Acetyltransferase Activity Mol. Endocrinol., April 1, 2002; 16(4): 824 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.J. Hodges and J.K. Chipman Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells Carcinogenesis, January 1, 2002; 23(1): 55 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Buckner, T. J. Moynihan, D. I. Quinn, U. Schlegel, F. Ali-Osman, K. Srivenugopal, R. Sawaya, M. Esteller, J. G. Herman, and J. N. Weinstein The DNA-Repair Gene MGMT and the Clinical Response of Gliomas to Alkylating Agents N. Engl. J. Med., March 1, 2001; 344(9): 686 - 688. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
