Carcinogenesis, Vol 19, 1487-1494, Copyright © 1998 by Oxford University Press
KL Steinmetz, IP Pogribny, SJ James and HC Pitot
DNA methylation at the 5-position on the cytosine ring in CpG dinucleotides
(CpG sites) appears to play an important role in regulating gene
expression. In general, there is an inverse relationship between promoter
CpG site methylation and the potential for transcription. Thus, changes in
DNA methylation density may lead to altered levels of proteins such as
glutathione S-transferase pi (GSTP), which is frequently used as a marker
to detect hepatocellular foci and neoplasms in the rat. In the present
study, the level of CpG methylation in the rat GSTP promoter region was
determined in bisulfite- treated DNA isolated from control (untreated) rat
livers, chemically induced, GSTP-positive rat liver neoplasms, and
methyl-deficient rat livers that contained numerous GSTP-positive foci
after administration of a defined diet deficient in folate and choline and
low in methionine (0.18%). Eight cytosines between -235 and + 140 in the
GSTP promoter region were methylated in a site-specific manner in
GSTP-negative control liver, whereas these same sites were hypomethylated
in all four chemically-induced, GSTP-positive neoplasms. Similarly, all CpG
sites were unmethylated in methyl-deficient liver DNA within 3 weeks of the
rats receiving the methyl-deficient diet, and they remained unmethylated
throughout the 36-week treatment period. Five of the eight CpG sites are
located within consensus sequences for the DNA binding proteins Spl and
E2F. This indicates at least one possible mechanism that could potentially
lead to transcriptional activation of GSTP in hepatocellular foci and
neoplasms during rat hepatocarcinogenesis. These findings suggest that
methylation of critical cytosines within the promoter region rather than
all CpG-associated cytosines may be a determining factor in regulation of
GSTP expression.
ARTICLES
Hypomethylation of the rat glutathione S-transferase pi (GSTP) promoter region isolated from methyl-deficient livers and GSTP-positive liver neoplasms
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706-1599, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Raychaudhuri, S. Raychaudhuri, M. Thamotharan, and S. U. Devaskar Histone Code Modifications Repress Glucose Transporter 4 Expression in the Intrauterine Growth-restricted Offspring J. Biol. Chem., May 16, 2008; 283(20): 13611 - 13626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. P. Pogribny, S. A. Ross, V. P. Tryndyak, M. Pogribna, L. A. Poirier, and T. V. Karpinets Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of Suv4-20h2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis induced by methyl deficiency in rats Carcinogenesis, June 1, 2006; 27(6): 1180 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Davis and E. O. Uthus DNA Methylation, Cancer Susceptibility, and Nutrient Interactions Experimental Biology and Medicine, November 1, 2004; 229(10): 988 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Detich, S. Hamm, G. Just, J. D. Knox, and M. Szyf The Methyl Donor S-Adenosylmethionine Inhibits Active Demethylation of DNA: A CANDIDATE NOVEL MECHANISM FOR THE PHARMACOLOGICAL EFFECTS OF S-ADENOSYLMETHIONINE J. Biol. Chem., May 30, 2003; 278(23): 20812 - 20820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ehrlich DNA Hypomethylation, Cancer, the Immunodeficiency, Centromeric Region Instability, Facial Anomalies Syndrome and Chromosomal Rearrangements J. Nutr., August 1, 2002; 132(8): 2424S - 2429. [Abstract] [Full Text] [PDF]
|
|