转基因后的转录激活和3D调节相互作用显示出对凝聚素枯竭的位置和分化特异性敏感性
UkJin Lee1,2, Alejandra Laguillo-Diego1, Wilfred Wong3,4
1Sanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA.
bioRxiv : the preprint server for biology
|March 4, 2025
概括
细胞分裂后大多数基因激活过程中,凝聚蛋白 (细胞分裂蛋白) 并不是必不可少的,但在细胞状态过渡过程中,特别是分化过程中,它对于建立特定的调节相互作用至关重要.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 之前的研究表明,在凝聚素耗尽时,结构循环会消失,而调节性增强剂-促进剂 (E-P) 循环会持续存在,在异步细胞中转录的影响最小.
- 由于异步细胞研究,素在细胞分裂和状态过渡期间建立调节相互作用和转录激活中的作用仍然不清楚.
研究的目的:
- 在小鼠胚胎干细胞 (ESC) 中的M-G1过渡过程中,研究凝聚素的需求,以建立调控相互作用和转录激活.
- 确定凝聚素在自我更新与分化环境中的作用,在转基因后的基因激活过程中.
主要方法:
- 在M-G1过渡期间,原始小鼠的ESC中,核心凝聚素子单位RAD21被耗尽.
- 细胞在自我更新条件下和形成性多能性 (EpiLC) 的分化过程中被分析.
- 评估了染色体相互作用,基因表达和表观遗传标记 (H3K27ac).
主要成果:
- 虽然大多数结构循环未能在没有凝聚力的情况下进行改革,但约有35%的监管循环被重新建立,通常与活性增强剂和H3K27ac标志相关.
- 转基因转移后的转录活性在很大程度上独立于凝聚素,很少有基因表现出受损的活性,主要是那些直接与RAD21结合的基因.
- 在分化过程中 (M-to-G1与EpiLC信号) 的凝聚素耗尽显示出更大的易感性,由于失败的*de novo*相互作用导致关键基因的激活受损.
结论:
- 凝聚蛋白对于大多数转基因转移后的转录活性是不必要的,但在细胞状态转换,特别是分化过程中建立特定的调节相互作用方面发挥着关键作用.
- 在凝聚蛋白,增强剂-促进剂相互作用和转录调节之间存在局部特异性和上下文特异性依赖.
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