GATA Factor-Mediated Gene Regulation in Human Erythropoiesis
Oriana Romano,
Luca Petiti,
Tristan Felix,
Vasco Meneghini,
Michel Portafax,
Chiara Antoniani,
Mario Amendola,
Silvio Bicciato,
Clelia Peano,
Annarita Miccio
Affiliations
Oriana Romano
Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
Luca Petiti
Institute of Biomedical Technologies, CNR, Milan, Italy
Tristan Felix
Laboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR, 1163 Paris, France
Vasco Meneghini
Laboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR, 1163 Paris, France
Michel Portafax
Laboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR, 1163 Paris, France
Chiara Antoniani
Laboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR, 1163 Paris, France
Mario Amendola
Genethon, INSERM UMR951, Evry, France
Silvio Bicciato
Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
Clelia Peano
Institute of Biomedical Technologies, CNR, Milan, Italy; Institute of Genetic and Biomedical Research, UOS Milan, National Research Council, Rozzano, Milan, Italy; Genomic Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy; Corresponding author
Annarita Miccio
Laboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM UMR, 1163 Paris, France; Paris Descartes, Sorbonne Paris Cité University, Imagine Institute, Paris, France; Corresponding author
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
