DNA Dioxygenases Tet2/3 Regulate Gene Promoter Accessibility and Chromatin Topology in Lineage-Specific Loci to Control Epithelial Differentiation

The study demonstrates that DNA dioxygenases Tet2 and Tet3 are crucial for regulating gene promoter accessibility and chromatin topology, essential for epithelial differentiation and hair formation. Using genetically engineered mice, researchers found that the absence of Tet2/3 leads to significant changes in hair structure, including sparse, short, and curly hair, eventually causing hair loss. Tet2/3-mediated DNA demethylation activates the Krt25 and Krt28 genes by increasing chromatin accessibility and facilitating the binding of transcription factors like Dlx3. These findings highlight the importance of Tet2/3 in hair keratin gene regulation and suggest potential therapeutic targets for hair growth abnormalities.