Publication by Boontanrart et al.: ATF4 regulates MYB to increase γ-globin in response to loss of β-globin.

Cellular stress prompts differentiating erythroid precursors to express high levels of fetal γ-globin. We discovered that decreased adult β-globin is sufficient to induce robust re-expression of γ-globin with ATF4 being a causal regulator of this response. The reduction of ATF4 upon β-globin ko decreases the levels of MYB and BCL11A. Our findings provide mechanistic insight to the phenomenon of stress-induced globin compensation and could inform strategies to treat hemoglobinopathies.