@article{4324ffb2230b4d3fa6c34926268c2fa5,
title = "A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells",
abstract = "The transcription factor Foxp3 participates dominantly in the specification and function of Foxp3+ CD4+ regulatory T cells (T reg cells) but is neither strictly necessary nor sufficient to determine the characteristic Treg cell signature. Here we used computational network inference and experimental testing to assess the contribution of other transcription factors to this. Enforced expression of Helios or Xbp1 elicited distinct signatures, but Eos, IRF4, Satb1, Lef1 and GATA-1 elicited exactly the same outcome, acting in synergy with Foxp3 to activate expression of most of the Treg cell signature, including key transcription factors, and enhancing occupancy by Foxp3 at its genomic targets. Conversely, the Treg cell signature was robust after inactivation of any single cofactor. A redundant genetic switch thus 'locked in' the T reg cell phenotype, a model that would account for several aspects of Treg cell physiology, differentiation and stability.",
author = "Wenxian Fu and Ayla Ergun and Ting Lu and Hill, {Jonathan A.} and Sokol Haxhinasto and Fassett, {Marlys S.} and Roi Gazit and Stanley Adoro and Laurie Glimcher and Susan Chan and Philippe Kastner and Derrick Rossi and Collins, {James J.} and Diane Mathis and Christophe Benoist",
note = "Funding Information: We thank R. Samstein and A. Rudensky for the unpublished ChIPseq data; S. Smale (University of California, Los Angeles) for mouse cDNA encoding Helios; M. Calderwood and the Center for Cancer Systems Biology for expression cDNA; P. Rahl for advice on ChIPSeq; J. Ericson, S. Davis, H. Paik and R. Cruse for genomic data analysis; H. Chen and Q. Cai for experimental support; and J. LaVecchio and G. Buruzala for sorting. This work benefited from public data generated by the Immunological Genome Project consortium. Supported by the US National Institutes of Health (AI051530 to C.B. and D.M.; AI072073 to C.B., D.M. and J.C.; training grant T32 DK7260 for support of M.S.F.; and 3R24AI07207303S1 for support of A.E.), GlaxoSmithKline, the Damon Runyon Cancer Research Foundation (S.H.), the American Diabetes Association (707BETA14 to W.F.) and the Canadian Institutes of Health Research (J.H.).",
year = "2012",
month = oct,
day = "1",
doi = "10.1038/ni.2420",
language = "English",
volume = "13",
pages = "972--980",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "10",
}