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<p>As a member of the hemoglobin family, γ-globin is usually persistently expressed at high levels to perform the oxygen-carrying function during fetal development. In recent years, related gene editing clinical trials have confirmed that reactivation of γ-globin expression is a promising therapeutic strategy for treating β-hemoglobinopathies, including β-thalassemia and sickle cell disease. Human γ-globin expression is finely regulated by multiple mechanisms, and a deeper understanding of the mechanisms will help develop drugs that target its activation. With the advancement of biotechnology, epigenetic modifications (EMs) and protein post-translational modifications (PPTMs) have shown irreplaceable roles in the regulation of γ-globin expression. Therefore, this review will comprehensively summarize the regulatory mechanisms of EMs and PPTMs on γ-globin to provide new ideas for the treatment of β-hemoglobinopathies.</p>

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Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月17日

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  • Dahang Ye,
  • Meihuan Chen,
  • Ying Zhu,
  • XinYuan Feng,
  • Liangpu Xu,
  • Hailong Huang

摘要

As a member of the hemoglobin family, γ-globin is usually persistently expressed at high levels to perform the oxygen-carrying function during fetal development. In recent years, related gene editing clinical trials have confirmed that reactivation of γ-globin expression is a promising therapeutic strategy for treating β-hemoglobinopathies, including β-thalassemia and sickle cell disease. Human γ-globin expression is finely regulated by multiple mechanisms, and a deeper understanding of the mechanisms will help develop drugs that target its activation. With the advancement of biotechnology, epigenetic modifications (EMs) and protein post-translational modifications (PPTMs) have shown irreplaceable roles in the regulation of γ-globin expression. Therefore, this review will comprehensively summarize the regulatory mechanisms of EMs and PPTMs on γ-globin to provide new ideas for the treatment of β-hemoglobinopathies.