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¹ Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, England, UK
² Leeds Institute of Molecular Medicine, University of Leeds, St. James’s University Hospital, Leeds LS9 7TF, England, UK
³ Laboratory for Transcriptional Regulation, Institute of Physical and Chemical Research Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama 230-0045, Japan
⁴ Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
⁵ Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003

CORRESPONDENCE Matthias Merkenschlager: matthias.merkenschlager{at}csc.mrc.ac.uk

Runx proteins are essential for hematopoiesis and play an important role in T cell development by regulating key target genes, such as CD4 and CD8 as well as lymphokine genes, during the specialization of naive CD4 T cells into distinct T helper subsets. In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at the protein level. We show that Runx proteins also regulate the initiation and the maintenance of Foxp3 gene expression in CD4 T cells. Full-length Runx promoted the de novo expression of Foxp3 during inducible T reg cell differentiation, whereas the isolated dominant-negative Runt DNA binding domain antagonized de novo Foxp3 expression. Foxp3 expression in natural T reg cells remained dependent on Runx proteins and correlated with the binding of Runx/core-binding factor β to regulatory elements within the Foxp3 locus. Our data show that Runx and Foxp3 are components of a feed-forward loop in which Runx proteins contribute to the expression of Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream target genes.

Abbreviations used: Cbfb, core-binding factor β; ChIP, chromatin immunoprecipitation; DMR, differentially methylated region; iT reg, induced T reg; mTOR, mammalian target of rapamycin; nT reg, natural T reg; PI3K, phosphatidyl inositol 3 kinase; RBS, Runx binding site.

© 2009 Bruno et al.
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• Bruno, L., Mazzarella, L., Hoogenkamp, M., Hertweck, A., Cobb, B. S., Sauer, S., Hadjur, S., Leleu, M., Naoe, Y., Telfer, J. C., Bonifer, C., Taniuchi, I., Fisher, A. G., Merkenschlager, M. (2009). Runx proteins regulate Foxp3 expression. JCB 187: i3-i3 [Full Text]  

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