Inhibiting the KIT-Src pathway to ensure differentiation of hematopoietic progenitor requires ARID4B [ChIP-seq]

Hematopoiesis is maintained by a highly regulated and hierarchical system, whereas aberrant control of hematopoiesis is the underlying cause of severe hematological diseases. Here, we demonstrate the indispensable role of ARID4B in fetal hematopoiesis that recruits Ezh2 to transcriptionally downregulate the expression of KIT during erythroid cell differentiation. Functional analyses reveal that the aberration of Arid4b inhibits fetal hematopoiesis at the multipotent progenitors (MPPs) stage, which reactivates the KIT-Src-family kinase (Src) pathway and leads to pre-mature erythroblast proliferation. The differentiation defect caused by ARID4B aberration could be counteracted by the Src inhibitor PP2 or by KIT knockdown. In summary, we identify ARID4B as a master regulator in the KIT-Src pathway, thus providing a fundamental insight in hematopoiesis and stem cell regulation. Overall design: K562 cells were used for ChIP, library preparation, sequencing, and initial data analysis. ChIP assays were performed using the anti-ARID4B antibody. Input DNA was used for control.