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- W4366183202 abstract "Execution of lineage-specific differentiation programs requires tight coordination between many regulators including Ten-eleven translocation (TET) family enzymes catalyzing 5-methylcytosine oxidation in DNA. Here, by using Keratin 14-Cre-driven ablation of Tet genes in skin epithelial cells, we demonstrate that ablation of Tet2/Tet3 result in marked alterations of hair shape and length followed by hair loss. Hair phenotype seen in Tet2/Tet3-deficient mice is consistent with the data published previously and showing that mutation in the KRT25 gene is associated with the wooly-hair syndrome and appearance of short, curly hairs in affected human individuals. By using whole-genome bisulfite sequencing, ATAQ-seq, ChIP-seq and RNA-seq analyses, we show that through DNA demethylation, Tet2/Tet3 control chromatin accessibility, Dlx3 binding and promoter activity of the Krt25 and Krt28 genes regulating hair shape, as well as regulate interactions between the Krt28 gene promoter and distal enhancer. By using HiC-seq chromosome conformation capture assay, we demonstrate that Tet2/Tet3 also control three-dimensional chromatin topology in Keratin type I/II gene loci via DNA methylation-independent mechanisms. These data demonstrate the essential roles for Tet2/3 in establishment of lineage-specific gene expression program and control of Dlx3/Krt25/Krt28 axis in hair follicle epithelial cells and implicate modulation of DNA methylation as a novel approach for hair growth control." @default.
- W4366183202 created "2023-04-19" @default.
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- W4366183202 date "2023-05-01" @default.
- W4366183202 modified "2023-09-28" @default.
- W4366183202 title "1440 DNA dioxygenases Tet2/3 regulate gene promoter accessibility and chromatin topology in lineage-specific loci to control keratinocyte differentiation and hair growth" @default.
- W4366183202 doi "https://doi.org/10.1016/j.jid.2023.03.1456" @default.
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