Chromatin-Remodeling Components of the BAF Complex Facilitate Reprogramming
Chromatin-Remodeling Components of the BAF Complex Facilitate Reprogramming
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DOI：
10.1016/j.cell.2010.04.037
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发表时间：
2010-06-11
期刊：
影响因子：
64.5
通讯作者：
Schoeler, Hans R.
中科院分区：
文献类型：
--
作者：
Singhal, Nishant;Graumann, Johannes;Schoeler, Hans R.
由Oct4、Sox2、Klf4和c-Myc四个转录因子组合实现的体细胞重编程效率很低。为了提高重新编程的效率和更好地了解过程，我们试图找出以更高的效率调节重新编程的因素。我们建立了一种从多能小鼠细胞提取物中筛选核部分的方法，该方法基于Oct4的重新激活。利用蛋白质组学，我们确定了依赖于ATP的BAF染色质重塑复合体的成分，当与四种因子一起使用时，它显著提高了重编程效率。重新编程的细胞可以传给生殖系，并表现出多能性。当c-Myc不存在但BAF组分过度表达时，重新编程仍然非常有效。BaF复合成分通过促进在重新编程过程中增强的Oct4与靶启动子的结合来介导这一效应。因此，使用染色质重塑分子的体细胞重编程是产生重编程细胞的一种有效方法。
Reprogramming of somatic cells achieved by combination of the four transcription factors Oct4, Sox2, Klf4, and c-Myc has very low efficiency. To increase the reprogramming efficiency and better understand the process, we sought to identify factors that mediate reprogramming with higher efficiency. We established an assay to screen nuclear fractions from extracts of pluripotent mouse cells based on Oct4 reactivation. Using proteomics, we identified components of the ATP-dependent BAF chromatin-remodeling complex, which significantly increases reprogramming efficiency when used together with the four factors. The reprogrammed cells could transmit to the germline and exhibited pluripotency. Reprogramming remained highly efficient when c-Myc was not present but BAF components were overexpressed. BAF complex components mediate this effect by facilitating enhanced Oct4 binding to target promoters during reprogramming. Thus, somatic cell reprogramming using chromatin-remodeling molecules represents an efficient method of generating reprogrammed cells.