多胞体抑制-脱基因酶复合体通过抑制多胞体活动来保护卵细胞表观基因组和女性生育能力
Jinwen Kang1,2, Peiyao Liu1,2, Shoko Ichimura1,2
1Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
bioRxiv : the preprint server for biology
|August 6, 2025
概括
聚抑制-脱基因酶 (PR-DUB) 复合物的BAP1组成部分保护卵细胞表观基因组. BAP1保护活跃的基因区域免受沉默,确保女性的生育能力和适当的胚胎发育.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 鼠标卵细胞具有独特的染色质结构,具有广泛的H3K27ac和H3K27me3域.
- 这种独特的卵细胞表观基因组背后的调节机制尚不清楚.
研究的目的:
- 为了研究BAP1的作用,一个组件的复杂的Polycomb抑制-deubiquitinase (PR-DUB),在调节卵细胞表观基因组.
- 为了确定BAP1在 oogenesis 过程中如何影响多合体活动和染色质景观.
主要方法:
- 在小鼠卵细胞中分析BAP1的功能.
- 对表观遗传修饰的研究,如H3K27ac,H3K27me3和H2AK119ub1.
- 在BAP1操纵后评估卵细胞发育能力和女性生育能力.
主要成果:
- BAP1作为卵细胞中Polycomb活动的负调节剂,限制H2AK119ub1的积累.
- BAP1保护卵细胞特定的H3K27ac域免受异位H3K27me3沉积,促进转录.
- 丢失BAP1会损害卵细胞的发育能力,母体转化为胚胎,以及早期胚胎发育,胚胎中持续存在异常H3K27me3.
结论:
- BAP1对于维护卵细胞表观基因组至关重要,它通过防止在 euchromatic 区域中异常的 Polycomb 活动.
- 在卵细胞中,BAP1的主要作用是转录激活,这对女性生育至关重要.
- 这项研究揭示了PR-DUB在保护卵细胞表观基因组方面的功能,而不仅仅是调解基因抑制.
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