title: Transcriptional regulation of the mouse IL-7 receptor alpha promoter by glucocorticoid receptor.
abstract: Expression of the IL-7R alpha-chain (IL-7Ralpha) is strictly regulated during the development and maturation of lymphocytes. Glucocorticoids (GC) have pleiotypic effects on the growth and function of lymphocytes. Although GC have been reported to induce the transcription of IL-7Ralpha gene in human T cells, its molecular mechanism is largely unknown. In this study, we show that GC up-regulate the levels of IL-7Ralpha mRNA and protein in mouse T cells. This effect does not require protein synthesis de novo, because protein synthesis inhibitors do not block the process. Mouse IL-7Ralpha promoter has striking homology with human and rat, containing consensus motifs of Ikaros, PU.1, and Runx1 transcription factors. In addition, a conserved noncoding sequence (CNS) of approximately 270 bp was found 3.6-kb upstream of the promoter, which was designated as CNS-1. A GC receptor (GR) motif is present in the CNS-1 region. Importantly, we show by reporter assay that the IL-7Ralpha promoter has specific transcription activity in T cells. This activity highly depends on the PU.1 motif. Furthermore, GC treatment augments the transcriptional activity through the GR motif in the CNS-1 region. We also demonstrate that GR binds to the GR motif by EMSA. In addition, by chromatin immunoprecipitation assay, we show that GR is rapidly recruited to endogenous CNS-1 chromatin after GC stimulation. These results demonstrate that GR binds to the GR motif in the CNS-1 region after GC stimulation and then activates the transcription of the IL-7Ralpha promoter. Thus, this study identifies the IL-7Ralpha CNS-1 region as a GC-responsive element.
authors.affiliation: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Hai-Chon
authors.initials: HC
authors.lastname: Lee
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shibata
authors.forename: Shinya
authors.initials: S
authors.lastname: Ogawa
authors.forename: Kazushige
authors.initials: K
authors.lastname: Maki
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D017124:Conserved Sequence; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D005819:Genetic Markers; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D002843:Chromatin; D003907:Dexamethasone; D005819:Genetic Markers; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D020395:Receptors, Interleukin-7; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C415350:interleukin-7 receptor, alpha chain