Nucleic Acids Research, 2002, Vol. 30, No. 9 1944-1951
© 2002 Oxford University Press
Control of IL-2R
gene expression: structural changes within the proximal enhancer/core promoter during T-cell development
INSERM U119-IFR57, 27 boulevard Lei Roure, 13009 Marseille, France, 1Centre d’Immunologie CNRS-INSERM-Univ. Med., 13288 Marseille Cedex 09, France and 2UPRES-EA 3290, Faculté de Médecine de la Timone, 27 bd Jean Moulin, 13385 Marseille Cedex 05, France
During T-cell development in thymus, CD25, the IL-2 receptor 
chain (IL-2R) is already expressed in early double-negative (DN) thymocytes where commitment to T-cell lineage has been established, but subsequently IL-2R is dramatically down-regulated for the remainder of T-cell development. The loss of IL-2R expression after expression of the pre-TCR :ß complex on the cell surface is essential for the later specific responses of mature T cells. Using appropriate mouse models and DMS genomic footprinting, we showed that the TATA box in the core promoter region of the murine IL-2R locus was occupied only in DN CD25+ T cells. Further, by chromatin immunoprecipitation assays, we evidenced that down-regulation of IL-2R transcription correlated with (i) loss of the basal transcriptional machinery; (ii) dissociation of histone acetylase p300 and BRG1, a member of the ATP-dependent chromatin remodeling complex SWI/SNF; and (iii) histone N-termini dephosphorylation plus deacetylation. In contrast, occupancy of the proximal enhancer region (positive regulatory region I) was not detected by in vivo genomic footprinting though constitutive accessibility of the promoter region for DNase I digestion both in the DN and double-positive stages correlated with the constitutive association of CBP and PCAF to the IL-2R core promoter. These results exemplify one mechanism by which a promoter enables transcription to switch on and off during T-cell differentiation.
* To whom correspondence should be addressed. Tel: +33 491 758 404; Fax: +33 491 260 364; Email: imbert{at}marseille.inserm.fr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Selvaraj, D. Bunick, C. Finnigan-Bunick, R. W. Johnson, H. Wang, L. Liu, and P. S. Cooke Gene Expression Profiling of 17{beta}-Estradiol and Genistein Effects on Mouse Thymus Toxicol. Sci., September 1, 2005; 87(1): 97 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Puthier, F. Joly, M. Irla, M. Saade, G. Victorero, B. Loriod, and C. Nguyen A General Survey of Thymocyte Differentiation by Transcriptional Analysis of Knockout Mouse Models J. Immunol., November 15, 2004; 173(10): 6109 - 6118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Gebuhr, G. I. Kovalev, S. Bultman, V. Godfrey, L. Su, and T. Magnuson The Role of Brg1, a Catalytic Subunit of Mammalian Chromatin-remodeling Complexes, in T Cell Development J. Exp. Med., December 15, 2003; 198(12): 1937 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chi, V. Senyuk, S. Chakraborty, and G. Nucifora EVI1 Promotes Cell Proliferation by Interacting with BRG1 and Blocking the Repression of BRG1 on E2F1 Activity J. Biol. Chem., December 12, 2003; 278(50): 49806 - 49811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Durda, I. S. Dunn, L. B. Rose, D. Butera, E. M. Benson, F. Pandolfi, and J. T. Kurnick Induction of "Antigen Silencing" in Melanomas by Oncostatin M: Down-Modulation of Melanocyte Antigen Expression Mol. Cancer Res., April 1, 2003; 1(6): 411 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Lemasson, N. J. Polakowski, P. J. Laybourn, and J. K. Nyborg Transcription Factor Binding and Histone Modifications on the Integrated Proviral Promoter in Human T-cell Leukemia Virus-I-infected T-cells J. Biol. Chem., December 13, 2002; 277(51): 49459 - 49465. [Abstract] [Full Text] [PDF]
|
|