PMID- 15665284
OWN - NLM
STAT- MEDLINE
DCOM- 20050302
LR  - 20081121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 65
IP  - 1
DP  - 2005 Jan 1
TI  - Expression-based discovery of variation in the human glutathione S-transferase M3 
      promoter and functional analysis in a glioma cell line using allele-specific 
      chromatin immunoprecipitation.
PG  - 99-104
AB  - Discovery and functional evaluation of biologically significant regulatory single 
      nucleotide polymorphisms (SNP) in carcinogen metabolism genes is a difficult 
      challenge because the phenotypic consequences may be both transient and subtle. 
      We have used a gene expression screening approach to identify a functional 
      regulatory SNP in glutathione S-transferase M3 (GSTM3). Anttila et al. proposed 
      that variation in GSTM3 expression was affected by exposure to cigarette smoke 
      and inheritance of the GSTM1-null genotype. To investigate the mechanism of GSTM3 
      expression was affected by exposure to cigarette smoke and inheritance of the 
      GSTM1-null genotype. To investigate the mechanism of GSTM3 expression variation, 
      we measured GSTM3 expression in lymphoblast cells from a human Centre d'Etude du 
      Polymorphisme Humain family and observed a low expression phenotype. Promoter 
      sequencing revealed two novel GSTM3 promoter SNPs: A/C and A/G SNPs, 63 and 783 
      bp upstream of the codon 1 start site, respectively. In this pedigree, the two 
      children homozygous for the -63C/C genotype had 8-fold lower GSTM3 expression 
      relative to the two children with the -63A/A genotype, with no association 
      between A-783G SNP and GSTM3 expression. Further evaluation using genotyped 
      glioma cell lines and with luciferase reporter constructs showed that the -63C 
      allele was associated with lower GSTM3 expression (P < 0.0001 and P < 0.003). RNA 
      pol II chromatin immunoprecipitation was combined with quantitative probed-based 
      allelic discrimination genotyping to provide direct evidence of a 9-fold reduced 
      RNA pol II binding capacity for the -63C allele. These results show that the 
      GSTM3 -63C allele strongly affects gene expression in human cell lines and 
      suggests that individuals who carry the low expression allele may be deficient in 
      glutathione transferase catalyzed biological functions.
FAU - Liu, Xuemei
AU  - Liu X
AD  - Laboratory of Computational Biology and Risk Analysis, National Institute of 
      Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
FAU - Campbell, Michelle R
AU  - Campbell MR
FAU - Pittman, Gary S
AU  - Pittman GS
FAU - Faulkner, Eric C
AU  - Faulkner EC
FAU - Watson, Mary A
AU  - Watson MA
FAU - Bell, Douglas A
AU  - Bell DA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Chromatin)
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Neoplasm)
RN  - EC 2.5.1.18 (GSTM3 protein, human)
RN  - EC 2.5.1.18 (Glutathione Transferase)
SB  - IM
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Chromatin/genetics
MH  - DNA Primers
MH  - DNA, Neoplasm/genetics
MH  - Female
MH  - Gene Expression Regulation, Enzymologic
MH  - Gene Expression Regulation, Neoplastic
MH  - Genetic Variation/*genetics
MH  - Genotype
MH  - Glioma
MH  - Glutathione Transferase/*genetics
MH  - Humans
MH  - Male
MH  - Pedigree
MH  - Phenotype
MH  - Polymerase Chain Reaction
MH  - Promoter Regions, Genetic/*genetics
EDAT- 2005/01/25 09:00
MHDA- 2005/03/03 09:00
CRDT- 2005/01/25 09:00
PHST- 2005/01/25 09:00 [pubmed]
PHST- 2005/03/03 09:00 [medline]
PHST- 2005/01/25 09:00 [entrez]
AID - 65/1/99 [pii]
PST - ppublish
SO  - Cancer Res. 2005 Jan 1;65(1):99-104.