A single nucleotide polymorphism in the proximal IFN-gamma promoter alters control of gene transcription.
Interferon-gamma (IFN-gamma) is an important cytokine that regulates cellular immune responses to intracellular pathogens and neoplasia. Regulation of IFN-gamma expression is stringently controlled at the transcriptional level. In this report we describe two novel single nucleotide polymorphisms (SNPs); one, at -179 in the promoter, occurs in 4% of African Americans. This SNP represents a guanidine to thymidine transition and creates a potential AP-1 binding element. Electrophoretic mobility shift analysis reveals a unique complex binding to an oligonucleotide containing the variant -179T but not to the -179G using nuclear extracts from human peripheral blood T cells. In reporter gene assays, T cell lines transfected with the variant -204(179T) IFN-gamma promoter show a six to 13-fold induction of luciferase activity in response to TNF-alpha over the common -204(179G) construct. The -179T allele identified in the proximal IFN-gamma promoter confers TNF-alpha inducibility and may prove important in human immune disorders and responsiveness to pathogens.
Bream
J H
JH
Laboratory of Experimental Immunology, SAIC-Frederick, NCI Frederick, Frederick, Maryland 21702-1201, USA.
Ping
A
A
Zhang
X
X
Winkler
C
C
Young
H A
HA
D000818:Animals; D044383:Black People / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005787:Gene Frequency; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D044465:White People / Q000235:genetics; D001741:Black or African American
D007371:Interferon-gamma