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Significance Proliferation and differentiation are inversely correlated processes in many biological systems. Pu.1 is an ETS family transcription factor that promotes proliferation of erythroid progenitors and blocks their terminal differentiation. Downregulation of Pu.1 in erythroid progenitors triggers their terminal differentiation. The current work investigates the DNA sequences and transcription factors that regulate Pu.1 expression in erythroid progenitors. The results show that Runx1, acting through an upstream regulatory element, controls Pu.1 transcription in erythroid progenitors. Moreover, genome-wide analyses show that Runx1 and Pu.1 play pivotal roles in shaping the chromatin landscape during early erythropoiesis. The importance of Runx1 and Pu.1 in erythroid progenitors is further demonstrated by finding that ectopic expression of either factor in erythroid progenitors leads to their immortalization.

Runx1 promotes murine erythroid progenitor proliferation and inhibits differentiation by preventing Pu.1 downregulation