The Gata2 3′-distal region is essential for IL-3 responsiveness in basophil and mast cell progenitors

The transcription factor GATA2 is highly expressed in mast cells and basophils and plays an important role in their development. We identified the Gata2 distal mast cell and basophil enhancer (G2DMBE), located 53 kb downstream of the murine Gata2 gene. G2DMBE is highly acetylated and bound by GATA2 in mast cells and basophils and is partially conserved in the human genome. G2DMBE deletion impaired interleukin-3 (IL-3)-dependent mast cell differentiation and basophil expansion. GATA2 expression increased at the mast cell and basophil progenitor stage, and this upregulation was attenuated by G2DMBE deletion. Consistently, expression of the IL-3 receptor β-chain genes Csf2rb and Csf2rb2 was also reduced in G2DMBE-deficient cells. These findings identify G2DMBE as a regulator of GATA2-dependent IL-3 responsiveness at the progenitor stage and provide a mechanism for sustaining lineage-specific transcriptional programs during mast cell and basophil development.