在多能细胞中,BMAL1-TRIM28独立于CLOCK抑制了可转移的元素
Amador Gallardo1,2,3, Efres Belmonte-Reche1,2,3, María Marti-Marimon4,5
1Centre for Genomics and Oncological Research (GENYO), Avenue de la Ilustración 114, 18016, Granada, Spain.
对于昼夜节律至关重要的一种蛋白质BMAL1在发育中起着新的作用. 它抑制胚胎发生过程中可转移的元素,防止过早衰老并保持健康的成年生活.
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
- 时间生物学 时间生物学
背景情况:
- 该BMAL1-CLOCK异构体通过负反调节昼夜基因转录.
- 在产前发育过程中,BMAL1缺乏导致过早衰老,这表明BMAL1在生理过程中发挥了非循环的作用.
研究的目的:
- 阐明胚胎发育期间BMAL1未知的非日间活动功能.
- 研究BMAL1在调节可转移元素中的作用及其对细胞全能性的影响.
主要方法:
- 在多能细胞中研究了BMAL1与TRIM28的相互作用.
- 分析了可转移元素的H3K9me3介导的抑制.
- 在BMAL1损失时评估了MERVL元素的转录激活和3D基因组组织.
主要成果:
- BMAL1与TRIM28相互作用,通过H3K9me3.3.抑制可转移元素.
- 丧失BMAL1功能导致广泛的MERVL元素激活和3D基因组重组.
- 缺少BMAL1的细胞会获得与强度相关的特征.
结论:
- 在胚胎发生过程中,BMAL1充当了跨体子的钟表独立的转录抑制剂.
- 产前的BMAL1-TRIM28活性可以通过控制转子素活性来预防成人过早衰老.
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