Chromatin Architectural Protein CTCF Controls Epidermal Barrier Formation, Hair Follicle Fate Maintenance, and Suppresses Inflammatory Responses in the Skin Epithelium

    Igor Malashchuk, J. Rudold, Tayyebeh Vafaee, K. Poterliwicz, Andrey A. Sharov, Michael Y. Fessing, Andrei N. Mardaryev, Vladimir A. Botchkarev
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    TLDR The protein CTCF is essential for skin development, maintaining hair follicles, and preventing inflammation.
    The document reports on the role of the chromatin architectural protein CTCF in skin epithelium development and maintenance. Researchers generated K14-CreER/Ctcf fl/fl mice to study the effects of Ctcf ablation. They found that Ctcf deletion during embryonic development led to issues with epidermal barrier formation, altered expression of genes associated with terminal differentiation, and the transformation of developing hair follicles into inter-follicular epidermis. In adult mice, Ctcf ablation resulted in changes to the epidermal barrier structure, immune cell infiltration, and ectopic expression of epidermal keratins in hair follicle epithelium. Microarray analyses indicated changes in gene expression related to keratinocyte differentiation, immune response, and tumorigenesis. ChIP-seq analyses showed CTCF binding predominantly to distal gene regulatory elements rather than gene promoters in epidermal keratinocytes. These findings suggest that CTCF is crucial for epidermal differentiation, skin barrier formation, hair follicle cell fate maintenance, and suppressing inflammatory responses in the skin.
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