Abstract
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.