Nanog Expression in Embryonic Stem Cells - An Ideal Model System to Dissect Enhancer Function

Bioessays. 2017 Dec;39(12):10.1002/bies.201700086. doi: 10.1002/bies.201700086. Epub 2017 Oct 4.

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.

Keywords: eRNAs; embryonic stem cells; higher order chromosome structure; looping; super-enhancers; transcriptional regulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Enhancer Elements, Genetic*
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Developmental*
  • Genetic Loci
  • Genome*
  • Histones / genetics
  • Histones / metabolism
  • Mice
  • Models, Genetic
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism*
  • Nanog Homeobox Protein / genetics*
  • Nanog Homeobox Protein / metabolism
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Histones
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse