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

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.

SUBMITTER: Zuklys S

PROVIDER: S-EPMC5033077 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Žuklys Saulius S Handel Adam A Zhanybekova Saule S Govani Fatima F Keller Marcel M Maio Stefano S Mayer Carlos E CE Teh Hong Ying HY Hafen Katrin K Gallone Giuseppe G Barthlott Thomas T Ponting Chris P CP Holländer Georg A GA

Nature immunology 20160822 10

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 ge ...[more]

PMID: 27548434

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