GATA2 regulates mast cell identity and responsiveness to antigenic stimulation by promoting chromatin remodeling at super-enhancers

Nat Commun. 2021 Jan 21;12(1):494. doi: 10.1038/s41467-020-20766-0.

Abstract

Mast cells are critical effectors of allergic inflammation and protection against parasitic infections. We previously demonstrated that transcription factors GATA2 and MITF are the mast cell lineage-determining factors. However, it is unclear whether these lineage-determining factors regulate chromatin accessibility at mast cell enhancer regions. In this study, we demonstrate that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both typical and super-enhancers at genes that respond to antigenic stimulation. We find that the number and densities of GATA2- but not MITF-bound sites at the super-enhancers are several folds higher than that at the typical enhancers. Our studies reveal that GATA2 promotes robust gene transcription to maintain mast cell identity and respond to antigenic stimulation by binding to super-enhancer regions with dense GATA2 binding sites available at key mast cell genes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens / immunology
  • Antigens / metabolism*
  • Cell Lineage / genetics
  • Cells, Cultured
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly / genetics*
  • Enhancer Elements, Genetic / genetics*
  • Female
  • GATA2 Transcription Factor / genetics*
  • GATA2 Transcription Factor / metabolism
  • Gene Expression Profiling / methods
  • Male
  • Mast Cells / immunology
  • Mast Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism

Substances

  • Antigens
  • Chromatin
  • GATA2 Transcription Factor
  • Gata2 protein, mouse
  • Microphthalmia-Associated Transcription Factor