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Nat Immunol. 2016 Oct;17(10):1206-1215. doi: 10.1038/ni.3537. Epub 2016 Aug 22.

Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells.

Author information

1
Department of Biomedicine, University Children's Hospital and University of Basel, Basel, Switzerland.
2
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
3
Department of Paediatrics and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
#
Contributed equally

Abstract

Thymic epithelial cell differentiation, growth and function depend on the expression of the transcription factor Foxn1; however, its target genes have never been physically identified. Using static and inducible genetic model systems and chromatin studies, we developed a genome-wide map of direct Foxn1 target genes for postnatal thymic epithelia and defined the Foxn1 binding motif. We determined the function of Foxn1 in these cells and found that, in addition to the transcriptional control of genes involved in the attraction and lineage commitment of T cell precursors, Foxn1 regulates the expression of genes involved in antigen processing and thymocyte selection. Thus, critical events in thymic lympho-stromal cross-talk and T cell selection are indispensably choreographed by Foxn1.

PMID:
27548434
PMCID:
PMC5033077
DOI:
10.1038/ni.3537
[Indexed for MEDLINE]
Free PMC Article

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