Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in β0-thalassemia/HbE

Reactivating of fetal hemoglobin (HbF; alpha 2 gamma 2) can ameliorate the severity of beta-thalassemia disease by compensating for adult hemoglobin deficiency in patients. Previously, microarray analysis revealed that zinc finger protein (ZNF)802 (also known as Juxta-posed with another zinc finger gene-1 (JAZF1)) was upregulated in human erythroblasts derived from adult peripheral blood compared with fetal liver-derived cells, implying a potential role as a HbF repressor. However, deficiency in ZNF802 induced by lentiviral shRNA in beta(0)-thalassemia/hemoglobinE erythroblasts had no effect on erythroblast proliferation and differentiation. Remarkably, the induction of HBG expression was observed at the transcriptional and translational levels resulting in an increase of HbF to 35.0 +/- 3.5%. Interestingly, the embryonic globin transcripts were also upregulated but the translation of embryonic globin was not detected. These results suggest ZNF802 might be a transcriptional repressor of the gamma-globin gene in adult erythroid cells.

Automated summary

This study found that ZNF802 may act as a transcriptional repressor of the gamma-globin gene in adult erythroid cells. Deficiency in ZNF802 induced induction of HBG expression and increased HbF levels in beta(0)-thalassemia/hemoglobinE erythroblasts.