Mechanisms of enhancer action: the known and the unknown

Genome Biol. 2021 Apr 15;22(1):108. doi: 10.1186/s13059-021-02322-1.


Differential gene expression mechanisms ensure cellular differentiation and plasticity to shape ontogenetic and phylogenetic diversity of cell types. A key regulator of differential gene expression programs are the enhancers, the gene-distal cis-regulatory sequences that govern spatiotemporal and quantitative expression dynamics of target genes. Enhancers are widely believed to physically contact the target promoters to effect transcriptional activation. However, our understanding of the full complement of regulatory proteins and the definitive mechanics of enhancer action is incomplete. Here, we review recent findings to present some emerging concepts on enhancer action and also outline a set of outstanding questions.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic*
  • Evolution, Molecular
  • Gene Expression Regulation*
  • Genome-Wide Association Study
  • Genomics / methods
  • Humans
  • Introns
  • Regulatory Sequences, Nucleic Acid
  • Signal Transduction
  • Transcriptional Activation


  • Chromatin
  • DNA-Binding Proteins