Erythroid commitment and differentiation are regulated by the coordinated action of a host of transcription factors, including GATA2 and GATA1. Here, we explored GATA-mediated transcriptional regulation through the integrative analysis of gene expression, chromatin modifications, and GATA factors' binding in human multipotent hematopoietic stem/progenitor cells, early erythroid progenitors, and late precursors. A progressive loss of H3K27 acetylation and a diminished usage of active enhancers and super-enhancers were observed during erythroid commitment and differentiation. GATA factors mediate transcriptional changes through a stage-specific interplay with regulatory elements: GATA1 binds different sets of regulatory elements in erythroid progenitors and precursors and controls the transcription of distinct genes during commitment and differentiation. Importantly, our results highlight a pivotal role of promoters in determining the transcriptional program activated upon erythroid differentiation. Finally, we demonstrated that GATA1 binding to a stage-specific super-enhancer sustains the expression of the KIT receptor in human erythroid progenitors.
GATA Factor-Mediated Gene Regulation in Human Erythropoiesis / Romano, O.; Petiti, L.; Felix, T.; Meneghini, V.; Portafax, M.; Antoniani, C.; Amendola, M.; Bicciato, S.; Peano, C.; Miccio, A.. - In: ISCIENCE. - ISSN 2589-0042. - 23:4(2020), p. 101018. [10.1016/j.isci.2020.101018]