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

Saulius Žuklys, Adam Handel, Saule Zhanybekova, Fatima Govani, Marcel Keller, Stefano Maio, Carlos E. Mayer, Hong Ying Teh, Katrin Hafen, Giuseppe Gallone, Thomas Barthlott, Chris P. Ponting, Georg A. Holländer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1206-1215
Number of pages10
JournalNature Immunology
Volume17
Issue number10
Early online date22 Aug 2016
DOIs
Publication statusPublished - Oct 2016

Keywords

  • TRANSCRIPTION FACTOR
  • REPERTOIRE SELECTION
  • EXPRESSION
  • PROTEIN
  • THYMOCYTES
  • PROLIFERATION
  • MEDULLA
  • PACKAGE
  • BETA
  • CCR7

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