A multiple redundant genetic switch locks in the transcriptional signature of T regulatory cells

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A multiple redundant genetic switch locks in the transcriptional signature of T regulatory cells

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Title: A multiple redundant genetic switch locks in the transcriptional signature of T regulatory cells
Author: Fu, Wenxian; Ergun, Ayla; Lu, Ting; Hill, Jonathan A.; Haxhinasto, Sokol; Fassett, Marlys S.; Gazit, Roi; Adoro, Stanley; Glimcher, Laurie; Chan, Susan; Kastner, Philippe; Rossi, Derrick; Collins, James J.; Mathis, Diane; Benoist, Christophe

Note: Order does not necessarily reflect citation order of authors.

Citation: Fu, W., A. Ergun, T. Lu, J. A. Hill, S. Haxhinasto, M. S. Fassett, R. Gazit, et al. 2013. “A multiple redundant genetic switch locks in the transcriptional signature of T regulatory cells.” Nature immunology 13 (10): 972-980. doi:10.1038/ni.2420. http://dx.doi.org/10.1038/ni.2420.
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Abstract: The transcription factor FoxP3 partakes dominantly in the specification and function of FoxP3+CD4+ T regulatory cells (Tregs), but is neither strictly necessary nor sufficient to determine the characteristic Treg signature. Computational network inference and experimental testing assessed the contribution of other transcription factors (TF). Enforced expression of Helios or Xbp1 elicited specific signatures, but Eos, Irf4, Satb1, Lef1 and Gata1 elicited exactly the same outcome, synergizing with FoxP3 to activate most of the Treg signature, including key TFs, and enhancing FoxP3 occupancy at its genomic targets. Conversely, the Treg signature was robust to inactivation of any single cofactor. A redundant genetic switch thus locks-in the Treg phenotype, a model which accounts for several aspects of Treg physiology, differentiation and stability.
Published Version: doi:10.1038/ni.2420
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698954/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717525
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