DNA Dioxygenases Tet1/2/3 Control Cell Differentiation in Hair Follicle Keratinocytes via Modulating BMP Signaling Pathway

In the study from September 2019, researchers investigated the role of DNA dioxygenases Tet1/2/3 in hair follicle development and cycling by examining their expression and the levels of 5-hydroxymethylcytosine (5hmC) in developing hair follicles and during the hair cycle. They used a conditional triple knockout (TKO) mouse model with Shh-Cre mediated ablation of all three Tet genes to demonstrate that the loss of Tet1/2/3 resulted in shorter hair shafts in bended hair types and an increase in the number of straight hairs. This phenotype was associated with a significant decrease in the expression of Bmpr1a/1b and pSmad1 in hair shaft keratinocytes (KCs) from TKO mice. Additionally, hMeDIP-seq and ChIPseq analyses revealed 5hmC peaks and enhancer activity at the Bmpr1b promoter and near Bmpr1a/2 genes, indicating that Tet-mediated DNA hydroxymethylation controls hair shaft-specific KC differentiation and hair shaft formation by regulating the transcription of Bmpr1a/1b/2 and the activity of adjacent enhancers.