Fig. 8: A schematic model of the molecular mechanism by which G9a represses fetal globin gene expression. | Nature Communications

Fig. 8: A schematic model of the molecular mechanism by which G9a represses fetal globin gene expression.

From: A specific G9a inhibitor unveils BGLT3 lncRNA as a universal mediator of chemically induced fetal globin gene expression

Fig. 8: A schematic model of the molecular mechanism by which G9a represses fetal globin gene expression.

Two major HbF repressors, BCL11A and ZBTB7A, recruit G9a onto the BGLT3 gene locus, where G9a facilities H3K9me2. G9a-mediated H3K9me2 recruits BCL11A and ZBTB7A onto the BGLT3 gene locus via CHD4, which may further enhance locus-specific H3K9me2. This positive feedback loop of enhancement of H3K9me2 at the BGLT3 gene locus ensures to repress BGLT3 lncRNA and subsequent fetal globin expression. RK-701 reactivates fetal globin by disrupting this G9a–BCL11A/ZBTB7A system by inhibiting the enzymatic activity of G9a.

Back to article page