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

Yapeng Li, Junfeng Gao, Mohammad Kamran, Laura Harmacek, Thomas Danhorn, Sonia M. Leach, Brian P. O’Connor, James R. Hagman and Hua Huang ()
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Yapeng Li: National Jewish Health
Junfeng Gao: National Jewish Health
Mohammad Kamran: National Jewish Health
Laura Harmacek: National Jewish Health
Thomas Danhorn: National Jewish Health
Sonia M. Leach: National Jewish Health
Brian P. O’Connor: National Jewish Health
James R. Hagman: National Jewish Health
Hua Huang: National Jewish Health

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20766-0

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