GATA Factor-Mediated Gene Regulation in Human Erythropoiesis

Autor: Oriana Romano, Luca Petiti, Tristan Felix, Vasco Meneghini, Michel Portafax, Chiara Antoniani, Mario Amendola, Silvio Bicciato, Clelia Peano, Annarita Miccio
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: iScience, Vol 23, Iss 4, Pp - (2020)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2020.101018
Popis: Summary: 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. : Biological Sciences; Molecular Biology; Molecular Mechanism of Gene Regulation; Cell Biology Subject Areas: Biological Sciences, Molecular Biology, Molecular Mechanism of Gene Regulation, Cell Biology
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