The histone methyltransferase MLL1 complex inhibits expression of fetal hemoglobin.

ABSTRACT: Increasing fetal-type hemoglobin expression in adult erythroid cells holds promise in the treatment of sickle cell disease (SCD) and β-thalassemia. We have identified the MLL1 complex as a critical regulator of fetal and embryonic hemoglobin repression. Knockdowns of MEN1 and KMT2A, encoding essential components of the complex, caused a significant downregulation of BCL11A expression and a substantial increase in γ- and ε-globin mRNA levels in HUDEP-2 cells. Significant binding of MEN1 and KMT2A was readily detected at the promoter and a critical enhancer of BCL11A in HUDEP-2 cells, suggesting that BCL11A is a direct transcriptional target of the MLL1 complex. Consistent with these results, MEN1 or KMT2A knockdown in normal human CD34⁺ hematopoietic stem and progenitor cells ind

SUBMITTER: Han Y 

PROVIDER: S-EPMC12670561 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature