Transcription Factor GATA2 Promotes Chromatin Remodeling at the Super-Enhancers of the Key Mast Cell Identity Genes and Primes Enhancers to Respond to Antigenic Stimulation [ATAC-seq]

Mast cells are critical effectors in causing allergic inflammation and in protecting against certain parasitic infections. We previously demonstrated that transcription factors GATA2 and MITF are the mast cell lineage-determining factors (LDTFs). However, it is unclear whether these LDTFs play a role in regulating chromatin accessibility at the enhancer regions. In this study, we demonstrate that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both the typical and super-enhancers at the genes that respond to antigenic stimulation. We found that the number and densities of GATA2, but not MITF, -bound sites at the super-enhancers were several folds higher than that at the typical enhancers. Our study reveals that GATA2 promotes robust gene transcription to maintain mast cell identity and respond to antigenic stimulation simply by binding to a larger number of GATA2 binding sites available at the super-enhancers of the key mast cell genes. Overall design: Omni-ATAC-seq in unstimulated or stimulated WT and Gata2 KO BMMCs, in duplicate, using Illumina NovaSEQ6000 platform.