DNA Dioxygenases Tet2/3 Regulate Gene Promoter Accessibility and Chromatin Topology in Lineage-Specific Loci to Control Keratinocyte Differentiation and Hair Growth
TLDR Tet2 and Tet3 enzymes are important for controlling hair growth and shape by affecting gene activity and DNA structure in hair follicles.
The study investigates the role of Tet2 and Tet3 enzymes in regulating keratinocyte differentiation and hair growth. Using Keratin 14-Cre-driven ablation of Tet genes in skin epithelial cells, researchers found that the absence of Tet2/Tet3 leads to significant changes in hair shape and length, resulting in hair loss. This phenotype is similar to the wooly-hair syndrome caused by KRT25 gene mutations. Through various sequencing techniques, the study shows that Tet2/Tet3 control chromatin accessibility, Dlx3 binding, and promoter activity of Krt25 and Krt28 genes, which are crucial for hair shape. Additionally, Tet2/Tet3 influence three-dimensional chromatin topology in Keratin type I/II gene loci through DNA methylation-independent mechanisms. The findings highlight the essential roles of Tet2/3 in gene expression and suggest that modulating DNA methylation could be a novel approach for controlling hair growth.
