College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou 225009, China.
Int J Mol Sci. 2022 Aug 22;23(16):9481. doi: 10.3390/ijms23169481.
Hair follicles (HFs) are organs that periodically regenerate during the growth and development of mammals. Long non-coding RNAs (lncRNAs) are non-coding RNAs with crucial roles in many biological processes. Our previous study identified that lncRNA2919 is highly expressed in catagen during the HF cycle. In this study, the in vivo rabbit model was established using intradermal injection of adenovirus-mediated lncRNA2919. The results showed that lncRNA2919 decreased HF depth and density and contributed to HF regrowth, thereby indicating that lncRNA2919 plays a negative role in HF regeneration. Moreover, methylation levels of the lncRNA2919 promoter at different HF cycle stages were detected through bisulfite sequencing. The key CpG site that negatively correlates with lncRNA2919 expression during the HF cycle was identified. 5-Aza-dc-induced demethylation upregulated lncRNA2919 expression, and the core promoter region of lncRNA2919 was verified on the basis of luciferase activity. Furthermore, we found that DNA methylation could prevent the binding of EGR1 to the lncRNA2919 promoter region, thereby affecting the transcriptional expression of lncRNA2919. Collectively, DNA methylation inhibits the transcriptional expression of lncRNA2919, which plays a vital role in the HF cycle and HF regrowth. These findings contribute to the basic theory of epigenetics in HF biology and provide references for further research in HF disease treatment and animal wool production.
毛囊(HFs)是哺乳动物生长发育过程中周期性再生的器官。长链非编码 RNA(lncRNA)是在许多生物学过程中发挥关键作用的非编码 RNA。我们之前的研究表明,lncRNA2919 在 HF 周期的退行期高度表达。在这项研究中,通过皮内注射腺病毒介导的 lncRNA2919 建立了体内兔模型。结果表明,lncRNA2919 降低了 HF 的深度和密度,并有助于 HF 再生,这表明 lncRNA2919 在 HF 再生中发挥负作用。此外,通过亚硫酸氢盐测序检测了不同 HF 周期阶段 lncRNA2919 启动子的甲基化水平。确定了与 HF 周期中 lncRNA2919 表达负相关的关键 CpG 位点。5-Aza-dc 诱导的去甲基化上调了 lncRNA2919 的表达,并基于荧光素酶活性验证了 lncRNA2919 的核心启动子区域。此外,我们发现 DNA 甲基化可以阻止 EGR1 与 lncRNA2919 启动子区域结合,从而影响 lncRNA2919 的转录表达。综上所述,DNA 甲基化抑制 lncRNA2919 的转录表达,在 HF 周期和 HF 再生中发挥重要作用。这些发现为 HF 生物学中的表观遗传学基础理论提供了依据,并为 HF 疾病治疗和动物羊毛生产的进一步研究提供了参考。