一个扩展的转录网络用于胚胎干细胞的多能性
Jonghwan Kim1, Jianlin Chu, Xiaohua Shen
1Department of Pediatric Oncology, Boston, MA 02115, USA.
Cell
|March 25, 2008
概括
研究人员绘制了控制胚胎干细胞多能性的关键转录因子. 他们发现,与基因促进体结合的因子数量决定了基因在分化过程中是否保持活跃或被抑制.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 转录因子网络是转录因子网络.
背景情况:
- 胚胎干细胞 (ES) 具有多能性,即能够分化为任何细胞类型.
- 已知只有有限数量的转录因子能够维持这种关键状态.
- 缺乏对管理多能性的监管网络的全面理解.
研究的目的:
- 全球识别小鼠ES细胞中九个关键转录因子的向促进体.
- 阐明维持多能性的监管网络.
- 了解转录因子在ES细胞命运决定中的作用.
主要方法:
- 全基因组识别转录因子结合部位.
- 对小鼠ES细胞中基因促进体的转录因子占用率的分析.
- 转录因子结合与基因活性和分化状态的相关性.
主要成果:
- 确定了Oct4,Sox2,Klf4,c-Myc,Nanog,Dax1,Rex1,Zpf281和Nac1.1的目标促进体.
- 证明由少数因子结合的促进子是不活跃的/被抑制的,而由>4个因子结合的促进子在多能细胞中是活跃的,并在分化时被抑制.
- 提出了重编程因子的转录层次,将c-Myc目标与其他目标区分开来.
结论:
- 与促进体结合的转录因子的数量是多能细胞中基因活性的关键决定因素.
- 一个复杂的转录网络,具有不同的角色的因素,如c-Myc,保持多能性.
- 这项研究为研究多能性和差异化背后的机制提供了宝贵的资源.
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