转录因子的协同绑定调节重编程
Constantinos Chronis1, Petko Fiziev1, Bernadett Papp1
1David Geffen School of Medicine, Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, Bioinformatics Program, Los Angeles, CA 90095, USA.
Cell
|January 24, 2017
概括
Oct4,Sox2,Klf4和cMyc (OSKM) 通过非活性化体力增强剂和选择多能增强剂来重新编程细胞. 这些过程由OSKM与特定阶段的转录因子相互作用来指导.
科学领域:
- 细胞重编程
- 表观遗传学
- 转录因子函数
背景情况:
- Oct4,Sox2,Klf4和cMyc (OSKM) 是诱导体细胞多能性的关键转录因子.
- 对于再生医学和发育生物学来说,了解OSKM调节的精确机制至关重要.
研究的目的:
- 在细胞重编程过程中阐明OSKM功能的机械细节.
- 在重编程过程中映射OSKM与染色体状态和阶段特异性转录因子的动态相互作用.
主要方法:
- 对OSKM结合部位,转录因子结合和染色质状态的全基因组映射.
- 功能损失和增益实验,以评估转录因子对重新编程效率的影响.
主要成果:
- OSK转录因子早期结合了活性体质增强剂,从而启动了它们的全基因组无活化.
- 人体转录因子的重新分配和Hdac1的招募伴随着人体增强剂的失活.
- 多能增强剂的选择是一个由OSK早期启动并由其他多能因素进一步调节的阶段性过程.
- 身体或多能性因子的过度表达会调节OSKM向和增强器动态,影响重编程效率.
结论:
- OSKM和特定阶段的转录因子之间的协作相互作用对于指导体质增强剂无活化和多能增强剂选择至关重要.
- 这些复杂的分子相互作用协调了复杂的细胞重编程过程.
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