Zhong Zhenyu, Bai Kangkang, Song Zhihao, Yang Mengxue, Li Minghao, Wang Shanhe, Wang Xin
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.
College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
Epigenetics Chromatin. 2025 Aug 8;18(1):52. doi: 10.1186/s13072-025-00611-8.
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.
毛囊的形态发生和发育从根本上依赖于表皮与真皮之间的相互作用，其中真皮乳头细胞（DPCs）在这些过程中起着关键作用。H3K4me3作为关键的组蛋白修饰之一，对于协调基因表达至关重要。然而，绒山羊DPCs中H3K4me3的表观遗传修饰图谱及其在毛囊发育中的作用机制仍未被探索。在本研究中，通过CUT&Tag技术绘制了H3K4me3的表观调控图谱。用H3K4me3抑制剂BCL-121和激动剂PBIT对DPCs进行外源处理。功能实验结果表明，提高H3K4me3水平可显著增强DPCs的增殖能力，并促进Wnt信号通路相关基因的表达。随后，探索了H3K4me3的调控机制，通过CUT&Tag和RNA-seq相关性分析筛选出H3K4me3在胚胎期调控的差异表达基因RSPO3。功能研究表明，RSPO3可促进DPCs增殖，抑制细胞凋亡，并增加Wnt信号通路相关基因的表达。综上所述，我们的研究结果表明，H3K4me3在DPCs中调控RSPO3的转录，这将为毛囊发育的分子机制奠定基础。
