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特定于血统的增强剂插入调节Prdm14,以推动动物从原始多能性快速过渡到形成多能性
Kazumi Matsubara1, Masaki Hirota1, Kentaro Kajiwara1
1Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Hyogo 6691337, Japan.
Development (Cambridge, England)
|November 21, 2025
概括
动物Prdm14表达是由独特的增强剂控制的,与其他哺乳动物不同. 这些监管要素确保了Prdm14的存在.
科学领域:
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 转录因子网络在多能转换期间动态重组.
- Prdm14 (含有14的PR/SET域) 对于多能性至关重要,但显示出特定物种的表达模式.
- 动物Prdm14在脱离纯粹的多能性后被下调,与非动物哺乳动物不同.
研究的目的:
- 为了研究动物特有的Prdm14表达背后的分子机制.
- 了解 cis 调节元件如何控制 Prdm14 在多能性期间的动态.
- 阐明Prdm14调节在脱离天真多能性的作用.
主要方法:
- 在CRISPR/Cas9中介的基因编辑中删除特定的cis-regulatory元素.
- 在原始胚胎干细胞中对Prdm14转录上调的分析.
- 对下游基因表达 (Pramel7,UHRF1) 和DNA脱甲基化的评估.
- 调查PRDM14结合动机破坏和反循环效应.
主要成果:
- 在Prdm14下游的Muroidea特有的cis-regulatory元素包含POU5F1和TFCP2L1识别点,这对于其在天真的ESC中进行上调至关重要.
- 这些增强剂的删除减少了Prdm14上调,Pramel7诱导和UHRF1降解,损害了DNA脱甲基化.
- 由于被破坏的负反循环,动物特异性增强剂中PRDM14结合动机的破坏延迟了原始到形成性的多能性过渡.
结论:
- 动物特有的增强剂插入为Prdm14创建了一个动态的调节架构,允许激活和抑制.
- 这种监管控制确保了早期胚胎发育中的天真多能性及时退出.
- 这些发现突出了基因调节在塑造发育过渡过程中的演变.
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