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.

Erythroid的承诺和分化受到包括GATA2和GATA1在内的许多转录因子的协同作用的调节。在这里，我们通过对人类多能造血干/祖细胞，早期红系祖细胞和晚期前体中基因表达，染色质修饰和GATA因子结合的综合分析，探索了GATA介导的转录调控。在类红素的定型和分化过程中，观察到了H3K27乙酰化的逐渐丧失以及活性增强剂和超级增强剂的使用减少。GATA因子通过与调节元件的特定阶段相互作用来介导转录变化：GATA1结合红系祖细胞和前体中的不同调控元件集，并在定型和分化过程中控制不同基因的转录。重要的是，我们的结果突出了启动子在确定红系分化后激活的转录程序中的关键作用。最后，我们证明了GATA1与阶段特异性超级增强子的结合维持了人类红系祖细胞中KIT受体的表达。