Activation, decommissioning, and dememorization: enhancers in a life cycle

Trends Biochem Sci. 2023 Aug;48(8):673-688. doi: 10.1016/j.tibs.2023.04.005. Epub 2023 May 21.

Abstract

Spatiotemporal regulation of cell type-specific gene expression is essential to convert a zygote into a complex organism that contains hundreds of distinct cell types. A class of cis-regulatory elements called enhancers, which have the potential to enhance target gene transcription, are crucial for precise gene expression programs during development. Following decades of research, many enhancers have been discovered and how enhancers become activated has been extensively studied. However, the mechanisms underlying enhancer silencing are less well understood. We review current understanding of enhancer decommissioning and dememorization, both of which enable enhancer silencing. We highlight recent progress from genome-wide perspectives that have revealed the life cycle of enhancers and how its dynamic regulation underlies cell fate transition, development, cell regeneration, and epigenetic reprogramming.

Keywords: cell fate; development; enhancer decommissioning; enhancer dememorization; epigenetic signatures.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Enhancer Elements, Genetic*
  • Life Cycle Stages*