Forever Young?

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Science  19 Dec 2008:
Vol. 322, Issue 5909, pp. 1753i
DOI: 10.1126/science.322.5909.1753i

Gamma-globin, a constituent of fetal hemoglobin, is normally expressed during fetal development. After birth, fetal hemoglobin expression is down-regulated when expression of the adult variant, β-globin, rises. Reliance of the adult on β-globin is not a problem, unless genetic defects disrupt the structure or function of β-globin, as is the case with some thalassemias and with sickle cell anemia. In such cases, the fetal variant, γ-globin, could potentially function as a replacement, except the γ-globin gene has usually been turned off by the process of globin gene switching. Sankaran et al. (p. 1839, published online 4 December; see the Perspective by Michelson) now show that the BCL11A gene, which encodes a putative transcription factor implicated in globin gene control, seems to function as a repressor of γ-globin gene expression. Use of small RNAs to knock down BCL11A expression in cultured erythroid cells resulted in increased γ-globin expression. Thus, BCL11A represents a target for interventions to treat sickle cell anemia and some thalassemias.

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