Identification of a novel glucocorticoid response unit (GRU) in the 5'-flanking region of the mouse IL-2 receptor alpha gene.
Glucocorticoid hormones inhibit the production of IL-2 and upregulate mouse interleukin 2 receptor alpha (IL-2Ralpha) gene expression in T cell lines by increasing its transcription rate. Now, the authors have used functional approaches to search for regulatory elements present in the 5'-flanking region of the IL-2Ralpha gene responsible for this effect. An important regulatory region was detected between -1382 and -1100 bp from the transcription initiation site. Within this region the authors characterized two 20 bp long cis-acting regulatory elements, named G1 and G2, which are involved in the modulation of the expression of the IL-2Ralpha gene by glucocorticoids. G1 contains a relatively well-conserved GRE half palindrome site, able to bind a partially purified glucocorticoid receptor but giving rise to an unstable complex. The G2 regulatory element contains no consensus sequences of binding sites for GR nor for any other described transcriptional factors but is able to form complexes with factors present in liver or T cells. Whereas G1 or G2 alone were unable to induce a glucocorticoid-response, the contiguous presence of G1 and G2 gave rise to an efficient response. Therefore, it is postulated that the glucocorticoid-induction of IL-2Ralpha gene is mediated, at least partly, through G1 and G2 elements which constitute a novel multicomponent glucocorticoid response unit (GRU).
Lamas
M
M
Departamento de Immunologia, Centro de Investigaciones Biologicas, CSIC, Madrid 28006, Spain.
Campos
J R
JR
Silva
A G
AG
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D009838:Oligodeoxyribonucleotides; 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; D015854:Up-Regulation / Q000187:drug effects*
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D009838:Oligodeoxyribonucleotides; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase