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Globin genes are regulated in a tissue-specific and developmental stage-specific manner, with the beta-globin gene being the last to be activated in the beta-gene cluster [1]. CACCC-nucleotide sequences, which bind multiple nuclear proteins, including ubiquitously expressed Sp1 and erythroid Kruppel-like factor (EKLF), are among the cis-regulatory sequences critical for transcription of globin and non-globin erythroid-expressed genes [2-5]. To determine the function of EKLF in vivo, we created mice deficient in EKLF by gene targeting [6]. These embryos die of anaemia during fetal liver erythropoiesis and show the molecular and haematological features of beta-globin deficiency, found in beta-thalassaemia. Although it is expressed at all stages, EKLF is not required for yolk sac erythropoiesis, erythroid commitment or expression of other potential target genes. Its stage-specific and beta-globin-gene-specific requirement suggests that EKLF may facilitate completion of the fetal-to-adult (haemoglobin gamma to beta) switch in humans.

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