Deletion of erythroid specific enhancer sequences delays embryonic and fetal globin gene silencing. (A) Fetal liver was dissected from indicated days of embryonic development. qPCR was done on RNA from the dissected tissue. Globin genes were normalized to GAPDH expression. Delayed hemoglobin switching of the mouse embryonic globins εy and βH1 was observed in Bcl11a(Δenh) mice. (B) Derepression of mouse embryonic globins (εy and βH1) in developmental erythropoiesis as assessed by qPCR. (C) Bcl11a(Δenh) mice were mated with β-YAC mice in order to evaluate human globin gene expression. Bcl11a(Δenh) mice failed to silence γ-globin gene expression during embryonic development. (D) qPCR analysis of RNA from 4-week and 22-week adult mice peripheral blood showed incomplete silencing of γ-globin. (E) Deletion of the in vitro defined core enhancer (+62DHS) region also fails to completely silence γ-globin; however, derepression is not to the level seen in Bcl11a(Δenh) mice. (Data are represented as mean ± standard error of the mean; ***P < .001; **P < .01; n.s., not significant; all conditions represent n ≥ 4.)