Chromatin Architectural Protein CTCF Regulates Terminal Keratinocyte Differentiation in the Developing Epidermis and Hair Follicles
TLDR CTCF protein is essential for skin and hair follicle development in mice.
The study investigated the role of the chromatin architectural protein CTCF in the development of the epidermis and hair follicles in mice. CTCF was found to be expressed in the developing skin and was associated with the regulation of genome organization, particularly at the borders of Topologically-Associating Domains (TADs) that contain keratin gene loci. The researchers created K14-Cre/Ctcf fl/fl mice with a targeted ablation of the Ctcf gene in keratinocytes. This ablation led to a significant decrease in CTCF protein in the developing epidermis and hair follicle epithelium, but not in the dermis or hair follicle mesenchyme. As a result, the mice exhibited a thinner epidermis, reduced keratinocyte proliferation, fewer hair follicles, and delayed hair follicle development compared to controls. RNA sequencing of primary keratinocytes from these mice showed changes in the expression of various epidermal and hair follicle-specific keratin genes, as well as an upregulation of embryonic epithelial keratin genes. These findings suggest that CTCF is crucial for terminal keratinocyte differentiation and the regulation of lineage-specific gene expression in keratinocytes.
