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<p>β-hemoglobinopathies, such as sickle cell disease and β-thalassemia, are common genetic disorders remaining significant global health challenges due to their associated morbidity and mortality. Increasing fetal hemoglobin (HbF) levels has emerged as a promising therapeutic strategy for these disorders. In this study, we report Myc-associated zinc finger (MAZ) as an indirect repressor of γ-globin (<i>HBG</i>) expression in human erythroid cells. Depletion of MAZ in HUDEP-2 and patient-derived β-thalassemia cells leads to significant inductions of both <i>HBG</i> mRNA and protein levels, resulting in increased HbF percentages and HbF + erythroid cells. We demonstrate that MAZ occupies at the promoter of MYB, a well-known <i>HBG</i> repressor. MAZ depletion reduced MYB levels. Restoration of MYB re-silenced the <i>HBG</i> levels in MAZ depleted cells. Our findings uncover the MAZ-MYB axis in <i>HBG</i> regulation, highlighting MAZ as a potential target to enhance HbF levels in patients with hemoglobin disorders.</p>

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MAZ regulates fetal hemoglobin repression by activating MYB transcription

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月2日

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  • Dian Lu,
  • Yinghong Yang,
  • Bo Yang,
  • Diyu Chen,
  • Mingming Zhu,
  • Siqi Huang,
  • Jun Hu,
  • Lifen Zhu,
  • Weimin Fan,
  • Yingjun Xie,
  • Bing Song,
  • Peng Huang,
  • Xiaofang Sun

摘要

β-hemoglobinopathies, such as sickle cell disease and β-thalassemia, are common genetic disorders remaining significant global health challenges due to their associated morbidity and mortality. Increasing fetal hemoglobin (HbF) levels has emerged as a promising therapeutic strategy for these disorders. In this study, we report Myc-associated zinc finger (MAZ) as an indirect repressor of γ-globin (HBG) expression in human erythroid cells. Depletion of MAZ in HUDEP-2 and patient-derived β-thalassemia cells leads to significant inductions of both HBG mRNA and protein levels, resulting in increased HbF percentages and HbF + erythroid cells. We demonstrate that MAZ occupies at the promoter of MYB, a well-known HBG repressor. MAZ depletion reduced MYB levels. Restoration of MYB re-silenced the HBG levels in MAZ depleted cells. Our findings uncover the MAZ-MYB axis in HBG regulation, highlighting MAZ as a potential target to enhance HbF levels in patients with hemoglobin disorders.