Actors with Multiple Roles: Pleiotropic Enhancers and the Paradigm of Enhancer Modularity

Trends Genet. 2019 Jun;35(6):423-433. doi: 10.1016/j.tig.2019.03.006. Epub 2019 Apr 18.

Abstract

The current paradigm in the field of gene regulation postulates that regulatory information for generating gene expression is organized into modules (enhancers), each containing the information for driving gene expression in a single spatiotemporal context. This modular organization is thought to facilitate the evolution of gene expression by minimizing pleiotropic effects. Here we review recent studies that provide evidence of quite the opposite: (i) enhancers can function in multiple developmental contexts, implying that enhancers can be pleiotropic, (ii) transcription factor binding sites within pleiotropic enhancers are reused in different contexts, and (iii) pleiotropy impacts the structure and evolution of enhancers. Altogether, this evidence suggests that enhancer pleiotropy is pervasive in animal genomes, challenging the commonly held view of modularity.

Keywords: enhancer; evolution; gene regulation; modularity; pleiotropy; transcription factor binding site.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Enhancer Elements, Genetic*
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental*
  • Genetic Loci
  • Genome
  • Organ Specificity
  • Protein Binding
  • Regulatory Sequences, Nucleic Acid
  • Transcription Factors / metabolism

Substances

  • Transcription Factors