DNA Dioxygenases TET Regulate Keratin Gene Expression and Enhancer Networks Within Lineage-Specific Gene Loci During Epidermal and Hair Follicle-Specific Keratinocyte Differentiation

    G. Chen, Qiling Xu, Michael Y. Fessing, Andrei N. Mardaryev, Andrey A. Sharov, Guanfeng Xu, Vladimir A. Botchkarev
    TLDR TET enzymes are important for skin and hair development by controlling gene activity in specific areas.
    In the study from May 1, 2021, researchers investigated the role of TET DNA dioxygenases in skin and hair follicle development by examining mice with a conditional knockout of Tet2 and Tet3 genes. They found that the absence of Tet2/3 led to a significant decrease in 5-hydroxymethylcytosine (5hmC) levels in the developing epidermis and hair follicles, as well as in hair matrix keratinocytes. This reduction was associated with altered epidermal differentiation, wavy hair, and subsequent hair loss when compared to wild-type and single knockout controls. RNA sequencing of cells from double knockout (DKO) mice showed changes in the expression of multiple epidermal and hair follicle-specific keratin genes. Additionally, these changes in gene expression were linked to alterations in H3K27ac enrichment and enhancer-promoter interactions within specific gene loci. The study concluded that TET enzymes play a complex role in the differentiation of epidermal and hair matrix keratinocytes by regulating gene promoters and enhancers in lineage-specific gene loci.
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