Core transcriptional regulatory circuitry in human embryonic stem cells
Core transcriptional regulatory circuitry in human embryonic stem cells
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DOI：
10.1016/j.cell.2005.08.020
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发表时间：
2005-09-23
期刊：
影响因子：
64.5
通讯作者：
Young, RA
中科院分区：
文献类型：
--
作者：
Boyer, LA;Lee, TI;Young, RA
转录因子OCT4、SOX 2和NANOG在早期发育中具有重要作用，并且是培养中未分化胚胎干（ES）细胞增殖所必需的。为了深入了解人类ES细胞的转录调控，我们使用基因组规模的位置分析确定了OCT 4，SOX 2和NANOG靶基因。令人惊讶的是，我们发现OCT 4、SOX 2和NANOG共同占据了它们靶基因的大部分。这些靶基因通常编码转录因子，其中许多是发育重要的同源结构域蛋白。我们的数据还表明，OCT 4，SOX 2和NANOG合作，形成由自动调节和前馈回路组成的调节回路。这些结果为干细胞的转录调控提供了新的见解，并揭示了OCT 4，SOX 2和NANOG如何有助于多能性和自我更新。
The transcription factors OCT4, SOX2, and NANOG have essential roles in early development and are required for the propagation of undifferentiated embryonic stem (ES) cells in culture. To gain insights into transcriptional regulation of human ES cells, we have identified OCT4, SOX2, and NANOG target genes using genome-scale location analysis. We found, surprisingly, that OCT4, SOX2, and NANOG co-occupy a substantial portion of their target genes. These target genes frequently encode transcription factors, many of which are developmentally important homeodomain proteins. Our data also indicate that OCT4, SOX2, and NANOG collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops. These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal.