Lethal β-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF

Andrew C. Parkins, Arlene H. Sharpe, Stuart H. Orkin

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501 Citations (Scopus)

Abstract

GLOBIN genes are regulated in a tissue-specific and developmental stage-specific manner, with the β-globin gene being the last to be activated in the β-gene cluster1. CACCC-nucleotide sequences, which bind multiple nuclear proteins, including ubiquitously expressed Spl and erythroid Krüppel-like factor (EKLF), are among the cis-regulatory sequences critical for transcription of globin and non-globin erythroid-expressed genes2-5. To determine the function of EKLF in vivo, we created mice deficient in EKLF by gene targeting6. These embryos die of anaemia during fetal liver erythropoiesis and show the molecular and haematological features of β-globin deficiency, found in β-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 β-globin-gene-specific requirement suggests that EKLF may facilitate completion of the fetal-to-adult (haemoglobin α to β) switch in humans.

Original languageEnglish
Pages (from-to)318-322
Number of pages5
JournalNature
Volume375
Issue number6529
DOIs
Publication statusPublished - 1995
Externally publishedYes

Keywords

  • EKLF
  • erythropoiesis
  • thalassaemia

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