H3K4me3 regulates the transcription of RSPO3 in dermal papilla cells to influence hair follicle morphogenesis and development

Morphogenesis and development of hair follicle fundamentally depend on the interaction between the epidermis and dermis, with dermal papilla cells (DPCs) playing a critical role in these processes. H3K4me3, one of the key histone modifications, is essential for coordinating gene expression. However, the epigenetic modification profile of H3K4me3 in cashmere goat DPCs and its mechanism of action in hair follicle development remain unexplored. In this study, the apparent regulation map of H3K4me3 was drawn by CUT&Tag technology. DPCs were exogenously treated with the H3K4me3 inhibitor BCL-121 and the agonist PBIT. Functional experiment results showed that increasing H3K4me3 levels significantly enhanced the proliferation capacity of DPCs and promoted the expression of Wnt signaling pathway-related genes. Subsequently, the regulatory mechanism of H3K4me3 was explored, and the differentially expressed gene RSPO3 in the embryonic stage regulated by H3K4me3 was screened through CUT&Tag and RNA-seq correlation analysis. Functional studies demonstrated that RSPO3 could promote DPCs proliferation, inhibit apoptosis, and increase the expression of genes related to the Wnt signaling pathway. In summary, our findings indicated that H3K4me3 regulates the transcription of RSPO3 in DPCs, which would lay the foundation for the molecular mechanism of hair follicle development.