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

被引：8

作者：

Wongborisuth, Chokdee ^{[1
,2
]}

Chumchuen, Sukanya ^{[2
]}

Sripichai, Orapan ^{[3
]}

Anurathaphan, Usanarat ^{[4
]}

Sathirapongsasuti, Nuankanya ^{[5
]}

Songdej, Duantida ^{[4
]}

Tangprasittipap, Amornrat ^{[2
]}

Hongeng, Suradej ^{[4
]}

机构：

[1] Mahidol Univ, Fac Sci, Multidisciplinary Unit, Program Mol Med, Bangkok, Thailand

[2] Mahidol Univ, Fac Med, Res Ctr, Ramathibodi Hosp, Bangkok, Thailand

[3] Minist Publ Hlth, Dept Med Sci, Natl Inst Hlth, Nonthaburi, Thailand

[4] Mahidol Univ, Fac Med, Dept Pediat, Ramathibodi Hosp, Bangkok, Thailand

[5] Mahidol Univ, Fac Med, Res Ctr, Sect Translat Med,Ramathibodi Hosp, Bangkok, Thailand

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

关键词：

ORPHAN NUCLEAR RECEPTORS; GLOBIN; EXPRESSION; TR2; INDUCTION; TARGET; BCL11A;

D O I：

10.1038/s41598-022-08920-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：8

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