Putting a finger on the switch

Abstract

The transition from fetal to adult beta-like globin expression is a key step in the maturation of the red blood cell lineage. Two new studies show that the KLF1 zinc finger protein uses direct and indirect means to regulate the final switch from fetal to adult globin expression and that monoallelic loss of KLF1 expression leads to persistence of fetal hemoglobin.

Figure 1

KLF1 regulates globin switching. During embryonic and fetal development or in KLF1-haploinsufficient adults (left), KLF1 levels are low, resulting in low levels of adult β-globin and BCL11A and high levels of γ-globin. In adults with two functional copies of KLF1 (right), increased expression of KLF1 in definitive red blood cells promotes high levels of adult β-globin and BCL11A expression, which in turn represses γ-globin expression.