Dataset Information

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

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 β⁰-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.

SUBMITTER: Wongborisuth C

PROVIDER: S-EPMC8943019 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in β<sup>0</sup>-thalassemia/HbE.

Wongborisuth Chokdee C Chumchuen Sukanya S Sripichai Orapan O Anurathaphan Usanarat U Sathirapongsasuti Nuankanya N Songdej Duantida D Tangprasittipap Amornrat A Hongeng Suradej S

Scientific reports 20220323 1

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 induce ...[more]

PMID: 35322124

Similar Datasets

Project description:BackgroundLow HbF expression in HbE-β+-thalassemia may lead to misdiagnosis of HbE heterozygosity. We aimed to characterize the β- and α-globin genes and the modifying factors related to HbF expression in patients with an Hb phenotype similar to that of HbE heterozygotes. Furthermore, screening tools for differentiating HbE-β+-thalassemia from HbE heterozygotes have been investigated.Participants and methodsA total of 2133 participants with HbE and HbA with varying HbF levels were recruited. Polymerase chain reaction-based DNA analysis and sequencing were performed to characterize β- and α-globin genes. DNA polymorphism at position -158 nt 5' to Gγ-globin was performed by XmnI restriction digestion. Receiver operating characteristic (ROC) curves were constructed using the area under the curve (AUC). Cutoff values of HbA2, HbE, and HbF levels for the differentiation of HbE-β+-thalassemia from HbE heterozygotes were determined.ResultsFive β+-thalassemia mutations trans to βE-gene (β-87(C>A), β-31(A>G), β-28(A>G), β19(A>G), and β126(T>G)) were identified in 79 patients. Among these, 54 presented with low HbF levels, and 25 presented with high HbF levels. ROC curve analysis revealed an excellent AUC of 1.000 (95% confidence interval:1.000-1.000) for HbE levels, and a cut-off point of ≥35.0% had 100.0% sensitivity, specificity, and Youden's index for differentiating HbE-β+-thalassemia from HbE heterozygotes. The proportion of α-thalassemia mutations was 46.3 and 8.0% among HbE-β+-thalassemia patients with low and high HbF levels, respectively. Two rare α-thalassemia mutations (Cap +14(C>G) and initiation codon (ATG>-TG)) of α2-globin genes were identified. The genotype and allele of the polymorphism at -158 nt 5' to Gγ-globin was found to be negatively associated with HbF expression.ConclusionsHbE-β+-thalassemia cannot be disregarded until appropriate DNA analysis is performed, and the detection of α-thalassemia mutations should always be performed under these conditions. An HbE level ≥35.0% may indicate screening of samples for DNA analysis for HbE-β+-thalassemia diagnosis.

Dataset Information

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

Publications

Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in β<sup>0</sup>-thalassemia/HbE.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Publications

Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in β<sup>0</sup>-thalassemia/HbE.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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