Down-regulation of the Transcriptional Repressor ZNF802 (JAZF1) Reactivates Fetal Hemoglobin in β-thalassemia/HbE

Overview

Journal Sci Rep

Specialty Science

Date 2022 Mar 24

PMID 35322124

Authors

Chokdee Wongborisuth

Sukanya Chumchuen

Orapan Sripichai

Usanarat Anurathaphan

Nuankanya Sathirapongsasuti

Duantida Songdej

Amornrat Tangprasittipap

Suradej Hongeng

Affiliations

Soon will be listed here.

Abstract

Reactivating of fetal hemoglobin (HbF; α2γ2) can ameliorate the severity of β-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 β-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 γ-globin gene in adult erythroid cells.

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