JBC INTERFERin siRNA transfection reagent

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M005447200 on August 14, 2000

J. Biol. Chem., Vol. 275, Issue 44, 34197-34204, November 3, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/44/34197    most recent
M005447200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bhakat, K. K.
Right arrow Articles by Mitra, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bhakat, K. K.
Right arrow Articles by Mitra, S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Regulation of the Human O6-Methylguanine-DNA Methyltransferase Gene by Transcriptional Coactivators cAMP Response Element-binding Protein-binding Protein and p300*

Kishor K. Bhakat and Sankar MitraDagger

From the Sealy Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555

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. 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 MGMT promoter are involved in activation by TSA. Ectopic expression of the transcriptional coactivators cAMP response element-binding protein-binding protein (CBP) and p300, which have intrinsic histone acetyltransferase 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 indicate that targeted histone acetylation results in the remodeling of chromatin by recruitment of the coactivator CBP/p300, and constitutes an important step in regulating MGMT expression.

* This work was supported by National Institutes of Health Grant R01 ES 07572.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Sealy Center for Molecular Science, University of Texas Medical Branch, 6.136 Medical Research Bldg., Rt. 1079, Galveston, TX 77555. Tel.: 409-772-1780; Fax: 409-747-8608; E-mail: samitra@utmb.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
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]

Home page
 Molecular Cancer TherapeuticsHome page
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]

Home page
 Mol Cancer ResHome page
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]

Home page
 CarcinogenesisHome page
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]

Home page
 Mol. Cell. Biol.Home page
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]

Home page
 CarcinogenesisHome page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 Mol. Endocrinol.Home page
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]

Home page
 CarcinogenesisHome page
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]

Home page
 NEJMHome page
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 TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.