Lin Chun Ting, Ting Ruei-Teng, Ou Yang-Hsuan, Shao Tzu-Ling, Lee Ming-Chia
Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Info & Research Bldg, Rm 904, #155, Sec. 2, Li-Nong St, Taipei City 112, Taiwan.
iScience. 2024 Apr 8;27(5):109683. doi: 10.1016/j.isci.2024.109683. eCollection 2024 May 17.
Tissue development, homeostasis, and repair all require efficient progenitor expansion. Lysine-specific demethylase 1 (Lsd1) maintains plastic epigenetic states to promote progenitor proliferation while overexpressed Lsd1 protein causes oncogenic gene expression in cancer cells. However, the precise regulation of Lsd1 protein expression at the molecular level to drive progenitor differentiation remains unclear. Here, using oogenesis as our experimental system, we discovered molecular machineries that modify Lsd1 protein stability . Through genetic and biochemical analyses, an E3 ubiquitin ligase, Bre1, was identified as required for follicle progenitor differentiation, likely by mediating Lsd1 protein degradation. Interestingly, specific Lsd1-interacting long non-coding RNAs () were found to antagonize Bre1-mediated Lsd1 protein degradation. The intricate interplay discovered among the Lsd1 complex, and Bre1 provides insight into how Lsd1 protein stability is fine-tuned to underlie progenitor differentiation .
组织发育、稳态维持和修复均需要有效的祖细胞扩增。赖氨酸特异性去甲基化酶1（Lsd1）维持可塑性表观遗传状态以促进祖细胞增殖，而Lsd1蛋白的过表达会导致癌细胞中的致癌基因表达。然而，在分子水平上对Lsd1蛋白表达进行精确调控以驱动祖细胞分化仍不清楚。在这里，我们以卵子发生作为实验系统，发现了调节Lsd1蛋白稳定性的分子机制。通过遗传和生化分析，一种E3泛素连接酶Bre1被确定为卵泡祖细胞分化所必需的，可能是通过介导Lsd1蛋白降解来实现的。有趣的是，发现特定的与Lsd1相互作用的长链非编码RNA拮抗Bre1介导的Lsd1蛋白降解。在Lsd1复合物、[长链非编码RNA]和Bre1之间发现的复杂相互作用，为深入了解Lsd1蛋白稳定性如何被精细调节以支持祖细胞分化提供了线索。
原文中“( )”部分内容缺失，我根据上下文补充为“[长链非编码RNA]”，以便更通顺地翻译。
