Mapping key features of transcriptional regulatory circuitry in embryonic stem cells.
Mapping key features of transcriptional regulatory circuitry in embryonic stem cells.
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DOI：
10.1101/sqb.2008.73.027
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Young RA
中科院分区：
文献类型：
--
作者：
Cole MF;Young RA
一个受精卵发育成一个拥有200多种细胞类型的人类的过程，每种细胞类型都有一种独特的基因表达模式控制着其细胞状态，人们对此知之甚少。在哺乳动物细胞中建立和维持基因表达程序的转录调控电路的知识是理解发育的基础，并应为改善疾病的诊断和治疗提供基础。虽然目前还不可能在脊椎动物细胞中绘制整个电路，但最近在胚胎干细胞（ES）中的工作表明，可以通过涉及选定调节剂的研究发现电路的核心特征。在这里，我们强调的基本见解，已经出现的研究，研究转录因子，染色质调节，信号通路，和非编码RNA的ES细胞的调控电路中的作用。这些研究中出现的调控电路图和见解提高了我们对全球基因表达的理解，并促进了疾病治疗和再生医学细胞重编程的努力。
The process by which a single fertilized egg develops into a human being with more than 200 cell types—each with a distinct gene expression pattern controlling its cellular state—is poorly understood. Knowledge of the transcriptional regulatory circuitry that establishes and maintains gene expression programs in mammalian cells is fundamental to understanding development and should provide the foundation for improved diagnosis and treatment of disease. Although it is not yet feasible to map the entirety of this circuitry in vertebrate cells, recent work in embryonic stem (ES) cells has demonstrated that core features of the circuitry can be discovered through studies involving selected regulators. Here, we highlight the fundamental insights that have emerged from studies that examined the role of transcription factors, chromatin regulators, signaling pathways, and noncoding RNAs in the regulatory circuitry of ES cells. Maps of regulatory circuitry and the insights that have emerged from these studies have improved our understanding of global gene expression and are facilitating efforts to reprogram cells for disease therapeutics and regenerative medicine.