Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Blood Research Institute, Blood Center of Wisconsin, 8733 West Watertown Plank Road, Milwaukee, WI 53226, USA.
Bioessays. 2017 Dec;39(12). doi: 10.1002/bies.201700086. Epub 2017 Oct 4.
Embryonic stem cells (ESCs) are derived from the preimplantation embryo and can differentiate into virtually any other cell type (termed pluripotency), which is governed by lineage specific transcriptions factors (TFs) binding to cis regulatory elements (CREs) to mediate changes in gene expression. The reliance on transcriptional regulation to maintain pluripotency makes ESCs a valuable model to study the role of distal CREs such as enhancers in modulating gene expression to affect cell fate decisions. This review will highlight recent advance on transcriptional enhancers, focusing on studies performed in ESCs. In addition, we argue that the Nanog locus, which encodes for an ESC-critical TF, is particularly informative because it contains multiple co-regulated genes and enhancers in close proximity to one another. The unique landscape at Nanog permits the study of ongoing questions including whether multiple enhancers function additively versus synergistically, determinants of gene specificity, and cell-to-cell variability in gene expression.
胚胎干细胞（ESCs）来源于着床前胚胎，可以分化为几乎任何其他细胞类型（称为多能性），这由谱系特异性转录因子（TFs）与顺式调控元件（CREs）结合来调节基因表达的变化来控制。依赖于转录调控来维持多能性使 ESCs 成为研究远端 CREs（如增强子）在调节基因表达以影响细胞命运决定中的作用的有价值的模型。这篇综述将重点介绍转录增强子的最新进展，主要集中在 ESCs 中的研究。此外，我们认为编码 ESC 关键 TF 的 Nanog 基因座特别有意义，因为它包含多个彼此靠近的共调控基因和增强子。Nanog 上的独特景观允许研究正在进行的问题，包括多个增强子是否以累加或协同方式发挥作用、基因特异性的决定因素以及基因表达的细胞间变异性。
