Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 3628K) PDF+supp data (9633K) PPT slides of all figures Supplemental Material Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Zamisch, M. Articles by Bosselut, R. PubMed PubMed Citation Articles by Zamisch, M. Articles by Bosselut, R. Social Bookmarking                            What's this?

¹ Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
² Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115
³ Laboratory of Tolerance and Autoimmunity, German Rheumatism Research Center (DRFZ), D-10117 Berlin, Germany

CORRESPONDENCE Rémy Bosselut: remy{at}helix.nih.gov

The transcription factor Ets1 contributes to the differentiation of CD8 lineage cells in the thymus, but how it does so is not understood. In this study, we demonstrate that Ets1 is required for the proper termination of CD4 expression during the differentiation of major histocompatability class 1 (MHC I)–restricted thymocytes, but not for other events associated with their positive selection, including the initiation of cytotoxic gene expression, corticomedullary migration, or thymus exit. We further show that Ets1 promotes expression of Runx3, a transcription factor important for CD8 T cell differentiation and the cessation of Cd4 gene expression. Enforced Runx3 expression in Ets1-deficient MHC I–restricted thymocytes largely rescued their impaired Cd4 silencing, indicating that Ets1 is not required for Runx3 function. Finally, we document that Ets1 binds at least two evolutionarily conserved regions within the Runx3 gene in vivo, supporting the possibility that Ets1 directly contributes to Runx3 transcription. These findings identify Ets1 as a key player during CD8 lineage differentiation and indicate that it acts, at least in part, by promoting Runx3 expression.

R. Grenningloh and Y. Xiong contributed equally to this paper.

L. Tian's present address is Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Pennington, NJ 08534

R. Grenningloh's present address is Autoimmune and Inflammatory Disease, Immunopharmacology, Merck Serono, Location A25/309, 64293 Darmstadt, Germany.

Abbreviations used: ChIP, chromatin immunoprecipitation; DP, double positive; SP, single positive; tRFP, tandem-dimer-tomato red fluorescent protein.

© 2009 The Rockefeller University Press
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS