Identification of an Intronic Regulatory Element Necessary for Tissue-Specific Expression of Foxn1 in Thymic Epithelial Cells

    Brian M. Larsen, Jennifer E. Cowan, Yueqiang Wang, Yu Tanaka, Yongge Zhao, Benjamin Voisin, Michael G. Constantinides, Keisuke Nagao, Yasmine Belkaid, Parirokh Awasthi, Yousuke Takahama, Avinash Bhandoola
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    TLDR A specific DNA region is crucial for Foxn1 gene expression in thymus cells but not in hair follicles.
    In this study, researchers identified a cis-regulatory element (RE) within the first intron of the Foxn1 gene that is essential for its expression in thymic epithelial cells but not in hair follicles. By systematically knocking out candidate regions, they pinpointed a 1.6 kb region whose deletion nearly abolished thymus development without affecting Foxn1 expression in hair follicles. This discovery was supported by chromatin accessibility, histone modifications, and sequence conservation analyses, and confirmed by RNA fluorescent in situ hybridization showing a significant loss of Foxn1 mRNA in the embryonic thymic bud. This RE was crucial for thymic-specific Foxn1 gene expression, highlighting its role in thymus development.
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