(Micro-C)Stage-specific erythroid cell three-dimensional chromatin architecture and transcription factors binding provide insight of human erythropoiesis

Mammalian red blood cells development can be divided into three period: hematopoietic stem and progenitor cells (HSPC), erythroid progenitor (Ery-Pro) and erythroid precursor (Ery-Pre). To better understand human erythropoiesis and its regulation, we performed genome-wide studies of chromatin architecture, enhancer and select transcription factors binding, and transcriptomics utilizing modified strategy to obtain defined progenitor and precursor populations from primary human erythroid cells. Integration and analysis of these data reveals that the TAD structure is stable but promoter-enhancer interactions are highly dynamic in a stage specific manner. Erythroid master regulator-GATA1 involves in the P-E interactions stepwisely. GATA1 binding is stable in erythroid progenitor-precursor, but dynamic GATA1 binding during this process regulate a productive erythroid gene expression and local chromatin rewiring. Additionally, we also show that dosage of GATA1 control the erythroid progenitor behavior and the erythroid progression. The valuable chromatin architecture and epigenome data will provide more comprehensive insight of human erythropoiesis and dynamic gene regulation of cell differentiation even more broadly.