Negative regulation of the interleukin (IL)-2 receptor alpha chain (CD25) promoter region in human B lymphocytes.
Studies of the CD25 gene promoter region in T cells have revealed the presence of a 31-bp region, including an 11-bp negative regulatory element (NRE), which profoundly suppresses CD25 expression. This report illustrates that the same region acts as a negative regulator of CD25 expression in human B lymphocytes. Human B cells contain DNA-binding protein activities which bind specifically to an oligonucleotide equivalent to the 11-bp core region of the NRE, and stimulation of tonsillar B cells or Daudi Burkitt's lymphoma B cells with interleukin 4 (IL-4) results in loss of binding activity for oligonucleotides containing the NRE; in contrast, IL-4 enhanced binding activity for the NRE in the Jurkat T cell line. Transient transfection analyses using deletion mutants lacking both the 11-bp core NRE and both the NRE and an adjacent putative retinoic acid response element (RARE) motif illustrated that the NRE element is a functional suppressor of CD25 transcription in B cells. Thus, deletion of the NRE element increased the basal level of CD25 promoter activity and also conferred IL-4 inducibility on reporter gene expression in transiently transfected tonsillar B lymphocytes.
Hewitt
E L
EL
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
Ozanne
B W
BW
Cushley
W
W
D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D019169:Jurkat Cells; D014066:Palatine Tonsil; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology
D004268:DNA-Binding Proteins; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D014212:Tretinoin; D015500:Chloramphenicol O-Acetyltransferase