FOXN1 remodels chromatin access and schedules fitness during thymus ontogeny

The transcription factor FOXN1 is essential for thymic epithelial cell development, function and maintenance. The spatiotemporal dynamics of its expression and the sequential activation of its target gene transcription during thymus organogenesis remain however undefined. Monitoring a fluorescent timer protein serving as a molecular “chronometer” transcriptionally controlled by the Foxn1 locus, we show that FOXN1 expression is spatially controlled during thymus development. Here, FOXN1 progressively opens and remodels the chromatin of its target genes. First supporting a stem and general epithelial cell gene expression profile, extended FOXN1 presence not only conditions the expression of genes indispensable for T cell development and selection but also coincides with the appearance of individual medullary islands. Hence, the length of FOXN1 expression determines a spatially controlled hierarchy of gene expression programs in thymic epithelial cells that orchestrate the capacity to support T lymphopoiesis and the initiation of the thymic medulla.