Transcriptional regulation of the thymus master regulator Foxn1

Abstract

FOXN1 is a transcription factor critical for the development of both thymic epithelial cell (TEC) and hair follicle cell (HFC) compartments. However, mechanisms controlling its expression remain poorly understood. To address this question, we performed thorough analyses of the evolutionary conservation and chromatin status of the Foxn1 locus in different tissues and states and identified several putative cis-regulatory regions unique to TECs versus HFCs. Furthermore, experiments using genetically modified mice with specific deletions in the Foxn1 locus and additional bioinformatic analyses helped us identify key regions and transcription factors involved in either positive or negative regulation of Foxn1 in both TECs and HFCs. Specifically, we identified SIX1 and FOXN1 itself as key factors inducing Foxn1 expression in embryonic and neonatal TECs. Together, our data provide important mechanistic insights into the transcriptional regulation of the Foxn1 gene in TEC versus HFC and highlight the role of FOXN1 in its autoregulation.

Comprehensive Transcriptomic Analysis for Thymic Epithelial Cells of Aged Mice and Humans

“…Furthermore, our investigation revealed significant epigenetic changes in both mouse and human TECs during aging, which can impact various aspects of TEC function and senescence. Previous studies have demonstrated the influence of epigenetic changes on the expression of Foxn1, the epithelial-to-mesenchymal transition of TECs to adipocytes, and the expression of tissue-restricted self-Ags ( 39 40 ). Moreover, our analysis also highlighted potential involvement of other unstudied epigenetic factors, such as histone methylation, histone acetylation, and DNA methylation, which may contribute to age-related TEC dysfunction.…”

Foxn1 is not essential for T‐cell development in teleosts

“…In the mammalian thymus, Foxn1 controls a complex genetic network [6–10], which ensures the generation of mature T cells expressing a diverse and self‐tolerant repertoire of T cell receptors. Foxn1 controls the expression of chemokine genes, such as Cxcl12 , which leads to the attraction of hematopoietic progenitors to the thymus anlage.…”