Models of human core transcriptional regulatory circuitries.
Models of human core transcriptional regulatory circuitries.
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DOI：
10.1101/gr.197590.115
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发表时间：
2016-03
期刊：
影响因子：
7
通讯作者：
Young RA
中科院分区：
文献类型：
--
作者：
Saint-André V;Federation AJ;Lin CY;Abraham BJ;Reddy J;Lee TI;Bradner JE;Young RA
在胚胎干细胞和其他研究充分的细胞模型中，一小组核心转录因子（TF）主导着基因表达程序的控制。这些核心转录因子共同调节它们自己的基因表达，从而形成一个相互连接的自动调节环，可以被认为是该细胞类型的核心转录调节回路（CRC）。对于大多数细胞类型，核心转录因子的知识有限，因此核心调控电路的模型也有限。我们最近发现，编码形成CRC的已知核心TF的基因是由超级增强子驱动的，这为通过超级增强子定位系统地预测研究不足的细胞类型中的CRC提供了机会。在这里，我们使用超级增强子图谱为75种人类细胞和组织类型生成CRC模型。这些核心电路模型应该证明有价值的进一步研究细胞类型特异性转录调控在健康和患病细胞。
A small set of core transcription factors (TFs) dominates control of the gene expression program in embryonic stem cells and other well-studied cellular models. These core TFs collectively regulate their own gene expression, thus forming an interconnected auto-regulatory loop that can be considered the core transcriptional regulatory circuitry (CRC) for that cell type. There is limited knowledge of core TFs, and thus models of core regulatory circuitry, for most cell types. We recently discovered that genes encoding known core TFs forming CRCs are driven by super-enhancers, which provides an opportunity to systematically predict CRCs in poorly studied cell types through super-enhancer mapping. Here, we use super-enhancer maps to generate CRC models for 75 human cell and tissue types. These core circuitry models should prove valuable for further investigating cell-type–specific transcriptional regulation in healthy and diseased cells.