Regulatory Landscaping: How Enhancer-Promoter Communication Is Sculpted in 3D

Mol Cell. 2019 Jun 20;74(6):1110-1122. doi: 10.1016/j.molcel.2019.05.032.

Abstract

During embryogenesis, precise gene transcription in space and time requires that distal enhancers and promoters communicate by physical proximity within gene regulatory landscapes. To achieve this, regulatory landscapes fold in nuclear space, creating complex 3D structures that influence enhancer-promoter communication and gene expression and that, when disrupted, can cause disease. Here, we provide an overview of how enhancers and promoters construct regulatory landscapes and how multiple scales of 3D chromatin structure sculpt their communication. We focus on emerging views of what enhancer-promoter contacts and chromatin domains physically represent and how two antagonistic fundamental forces-loop extrusion and homotypic attraction-likely form them. We also examine how these same forces spatially separate regulatory landscapes by functional state, thereby creating higher-order compartments that reconfigure during development to enable proper enhancer-promoter communication.

Publication types

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

MeSH terms

  • Animals
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Chromatin / metabolism
  • Chromatin / ultrastructure*
  • Embryo, Mammalian
  • Embryonic Development / genetics
  • Enhancer Elements, Genetic*
  • Eukaryotic Cells / metabolism
  • Eukaryotic Cells / ultrastructure
  • Gene Expression Regulation, Developmental*
  • Genome*
  • Humans
  • Molecular Conformation
  • Promoter Regions, Genetic*
  • Transcription, Genetic*

Substances

  • Chromatin