Global transcriptions upon MAZ knockdown HUDEP-2 cells
Hemoglobinopathies, such as sickle cell disease and ß-thalassemia, are common genetic disorders remaining significant global health challenges due to their associated morbidity and mortality. Increasing fetal hemoglobin (HbF) levels has emerged as a promising therapeutic strategy for these disorders. In this study, we report MAZ as a repressor of ?-globin expression in human erythroid cells. Depletion of MAZ in HUDEP-2 and patient-derived ß-thalassemia cells leads to significant inductions both of ?-globin mRNA and protein levels, resulting in increased HbF percentages and HbF+ erythroid cells. We demonstrate that MAZ occupies at the MYB promoter. MAZ depletion reduced MYB and BCL11A levels. Restoration of MYB re-silenced the ?-globin levels in MAZ depleted cells. Our findings uncover the MAZ-MYB axis in ?-globin regulation, highlighting MAZ as a potential target to enhance HbF levels in patients with hemoglobin disorders. Overall design: To investigate the role of MAZ in ?-globin regulation, we employed shRNAs to knockdown MAZ in a human adult-type erythroid cell line HUDEP-2. We performed RNA-seq to measure global transcriptions upon MAZ knockdown HUDEP-2 cells.