|
|
||||||||
Promoter by Glucocorticoid Receptor1
Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan
Expression of the IL-7R
-chain (IL-7R
) 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-7R
gene in human T cells, its molecular mechanism is largely unknown. In this study, we show that GC up-regulate the levels of IL-7R
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-7R
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
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-7R
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-7R
promoter. Thus, this study identifies the IL-7R
CNS-1 region as a GC-responsive element.
This article has been cited by other articles:
![]() |
H.-C. Lee, M. B. Headley, M. Iseki, K. Ikuta, and S. F. Ziegler Cutting Edge: Inhibition of NF-{kappa}B-Mediated TSLP Expression by Retinoid X Receptor J. Immunol., October 15, 2008; 181(8): 5189 - 5193. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Chandele, N. S. Joshi, J. Zhu, W. E. Paul, W. J. Leonard, and S. M. Kaech Formation of IL-7R{alpha}high and IL-7R{alpha}low CD8 T Cells during Infection Is Regulated by the Opposing Functions of GABP{alpha} and Gfi-1 J. Immunol., April 15, 2008; 180(8): 5309 - 5319. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Ma, S. Pathak, L. Trinh, and R. Lu Interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to down-regulate pre-B-cell receptor and promote cell-cycle withdrawal in pre-B-cell development Blood, February 1, 2008; 111(3): 1396 - 1403. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Vranjkovic, A. M. Crawley, K. Gee, A. Kumar, and J. B. Angel IL-7 decreases IL-7 receptor {alpha} (CD127) expression and induces the shedding of CD127 by human CD8+ T cells Int. Immunol., December 1, 2007; 19(12): 1329 - 1339. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. P. DeKoter, B. L. Schweitzer, M. B. Kamath, D. Jones, H. Tagoh, C. Bonifer, D. A. Hildeman, and K. J. Huang Regulation of the Interleukin-7 Receptor {alpha} Promoter by the Ets Transcription Factors PU.1 and GA-binding Protein in Developing B Cells J. Biol. Chem., May 11, 2007; 282(19): 14194 - 14204. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-C. Lee and S. F. Ziegler Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NF{kappa}B PNAS, January 16, 2007; 104(3): 914 - 919. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |