RESUMEN
Reactivating of fetal hemoglobin (HbF; α2γ2) can ameliorate the severity of ß-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 ß0-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.
Asunto(s)
Talasemia , Talasemia beta , Adulto , Proteínas Co-Represoras/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo/genética , Eritroblastos/metabolismo , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismo , Humanos , Factores de Transcripción/metabolismo , gamma-Globinas/genética , gamma-Globinas/metabolismoRESUMEN
Human iPSC line MU011.A-hiPS was generated from homozygous α-thalassemia (-(SEA)/-(SEA)) fetal skin fibroblasts using a non-integrative reprogramming method. Reprogramming factors OCT3/4, SOX2, KLF4, L-MYC, LIN28, and shRNA of TP53 contained in three episomal vectors were delivered using electroporation.