DNA Dioxygenases Tet1/2/3 Control Hair Matrix Keratinocyte Differentiation and Hair Shaft Shape via Regulation of Hair Keratin Gene Expression

    G. Chen, Qiling Xu, Michael Y. Fessing, Andrei N. Mardaryev, Andrey A. Sharov, Guanfeng Xu, Vladimir A. Botchkarev
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    TLDR The enzymes Tet1, Tet2, and Tet3 are important for the development of hair follicles and determining hair shape by controlling hair keratin genes.
    The study demonstrated that the DNA dioxygenases Tet1, Tet2, and Tet3 play a crucial role in hair follicle development and hair cycle by regulating the differentiation of hair matrix keratinocytes and the shape of the hair shaft through the control of hair keratin gene expression. The researchers observed dynamic changes in 5-hydroxymethylcytosine (5hmC) levels and Tet proteins in developing hair follicles. Using genetically modified mice with targeted ablation of Tet genes, they found that the absence of Tet2 and Tet3, or all three Tet enzymes, led to wavy hair and hair loss, as well as smaller hair bulbs and altered hair shape. RNA sequencing of primary keratinocytes from these mice showed a significant decrease in the expression of inner root sheath keratin genes, confirming the importance of Tet-mediated 5hmC DNA oxidation in hair keratinocyte differentiation and hair shaft morphology.
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