Transcriptional programmes underlying cellular identity and microbial responsiveness in the intestinal epithelium

Nat Rev Gastroenterol Hepatol. 2021 Jan;18(1):7-23. doi: 10.1038/s41575-020-00357-6. Epub 2020 Oct 6.

Abstract

The intestinal epithelium serves the unique and critical function of harvesting dietary nutrients, while simultaneously acting as a cellular barrier separating tissues from the luminal environment and gut microbial ecosystem. Two salient features of the intestinal epithelium enable it to perform these complex functions. First, cells within the intestinal epithelium achieve a wide range of specialized identities, including different cell types and distinct anterior-posterior patterning along the intestine. Second, intestinal epithelial cells are sensitive and responsive to the dynamic milieu of dietary nutrients, xenobiotics and microorganisms encountered in the intestinal luminal environment. These diverse identities and responsiveness of intestinal epithelial cells are achieved in part through the differential transcription of genes encoded in their shared genome. Here, we review insights from mice and other vertebrate models into the transcriptional regulatory mechanisms underlying intestinal epithelial identity and microbial responsiveness, including DNA methylation, chromatin accessibility, histone modifications and transcription factors. These studies are revealing that most transcription factors involved in intestinal epithelial identity also respond to changes in the microbiota, raising both opportunities and challenges to discern the underlying integrative transcriptional regulatory networks.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Differentiation / physiology
  • Cellular Microenvironment / genetics
  • Cellular Microenvironment / physiology*
  • Gastrointestinal Microbiome* / genetics
  • Gastrointestinal Microbiome* / physiology
  • Gene Expression Regulation
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / physiology*
  • Intestines / microbiology
  • Intestines / physiology
  • Mice
  • Models, Animal
  • Nutrigenomics
  • Nutritional Physiological Phenomena / genetics
  • Nutritional Physiological Phenomena / physiology
  • Transcription, Genetic / genetics
  • Transcription, Genetic / physiology
  • Zebrafish