Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease

Nat Commun. 2014 Sep 24;5:4907. doi: 10.1038/ncomms5907.

Abstract

How stage-specific enhancer dynamics modulate gene expression patterns essential for organ development, homeostasis and disease is not well understood. Here, we addressed this question by mapping chromatin occupancy of GATA4--a master cardiac transcription factor--in heart development and disease. We find that GATA4 binds and participates in establishing active chromatin regions by stimulating H3K27ac deposition, which facilitates GATA4-driven gene expression. GATA4 chromatin occupancy changes markedly between fetal and adult heart, with a limited binding sites overlap. Cardiac stress restored GATA4 occupancy to a subset of fetal sites, but many stress-associated GATA4 binding sites localized to loci not occupied by GATA4 during normal heart development. Collectively, our data show that dynamic, context-specific transcription factors occupancy underlies stage-specific events in development, homeostasis and disease.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cardiomegaly / metabolism*
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Enhancer Elements, Genetic / genetics
  • GATA4 Transcription Factor / metabolism*
  • Gene Expression Regulation, Developmental / physiology*
  • Heart / embryology*
  • High-Throughput Nucleotide Sequencing
  • Histones / metabolism
  • Luciferases
  • Mice
  • Mice, Transgenic
  • Morphogenesis / physiology*
  • Real-Time Polymerase Chain Reaction
  • Statistics, Nonparametric

Substances

  • Chromatin
  • GATA4 Transcription Factor
  • Gata4 protein, mouse
  • Histones
  • Luciferases

Associated data

  • GEO/GSE52123