4.7 Article

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

Journal

NATURE IMMUNOLOGY
Volume 17, Issue 10, Pages 1206-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3537

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Funding

  1. Swiss National Foundation [3100-68310.02, 3100-122558]
  2. Wellcome Trust [105045/Z/14/Z, 100643/Z/12/Z]
  3. European Commission [261387]
  4. Medical Research Council [MC_UU_12008/1] Funding Source: researchfish
  5. National Institute for Health Research [ACF-2011-18-008, CL-2016-13-001] Funding Source: researchfish
  6. Wellcome Trust [100643/Z/12/Z] Funding Source: Wellcome Trust
  7. MRC [MC_UU_12008/1] Funding Source: UKRI

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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.

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