HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Riera-Sans, L. Articles by Behrens, A. Search for Related Content PubMed PubMed Citation Articles by Riera-Sans, L. Articles by Behrens, A.

Regulation of / T Cell Development by the Activator Protein 1 Transcription Factor c-Jun¹

Mammalian Genetics Laboratory, Lincoln’s Inn Fields Laboratories, London Research Institute, Cancer Research, London, United Kingdom

c-Jun is a member of the AP-1 family of transcription factors, the activity of which is strongly augmented by TCR signaling. To elucidate the functions of c-Jun in mouse thymic lymphopoiesis, we conditionally inactivated c-Jun specifically during early T cell development. The loss of c-Jun resulted in enhanced generation of T cells, whereas T cell development was partially arrested at the double-negative 3 stage. The increased generation of T cells by loss of c-Jun was cell autonomous, because in a competitive reconstitution experiment the knockout-derived cells produced more T cells than did the control cells. C-jun-deficient immature T cells failed to efficiently repress transcription of IL-7R, resulting in augmented IL-7R mRNA and surface levels. Chromatin immunoprecipitation assays revealed binding of c-Jun to AP-1 binding sites present in the IL-7R promoter, indicating direct transcriptional regulation. Thus, c-Jun controls the transcription of IL-7R and is a novel regulator of the / T cell development.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ The London Research Institute is funded by Cancer Research U.K. L.R.-S. acknowledges support from an European Union Marie-Curie fellowship.

² Current address: Epithelial Homeostasis and Cancer, Department of Cell Differentiation and Cancer, Center of Genomic Regulation, Doctor Aiguader 88, 08003 Barcelona, Spain.

³ Address correspondence and reprint requests to Dr. Axel Behrens, Cancer Research U.K. London Research Institute, Lincoln’s Inn Fields Laboratories, Mammalian Genetics Laboratory, 44, Lincoln’s Inn Fields, London WC2A 3PX, U.K. E-mail address: axel.behrens{at}cancer.org.uk

⁴ Abbreviations used in this paper: DN, double negative; BM, bone marrow; DAPI, 4',6'-diamidino-2-phenylindole; ChIP, chromatin immunoprecipitation; FTOC, fetal thymus organ culture.

This article has been cited by other articles:

				V. J. Lawson, D. Maurice, J. D. Silk, V. Cerundolo, and K. Weston Aberrant Selection and Function of Invariant NKT Cells in the Absence of AP-1 Transcription Factor Fra-2 J. Immunol., August 15, 2009; 183(4): 2575 - 2584. [Abstract] [Full Text] [PDF]