Structure and evolution of a human erythroid transcription factor

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Abstract
VERTEBRATE erythroid cells contain a tissue-specific transcription factor referred to as Eryf 1 (ref. 1), GF-1 (ref. 2) or NF-E1 (ref. 3), for which binding sites are widely distributed in the promoters and enhancers of the globin gene family1–8, and of other erythroid-specific genes9,10. Aberrant binding of the human factor to a mutant site has been implicated in one form of hereditary persistence of fetal haemoglobin (HPFH; ref. 2). The complementary DNAs for both the chicken cEryfl (ref. 11) and mouse mEryf 1 (ref. 12) encoding genes have recently been cloned. We report here the cloning of the cDNA for the human Eryf 1 encoding gene. The central third of the hEryf 1 cDNA, containing two 'finger' motifs, is almost identical to that of chicken or mouse. The amino- and carboxy-terminal thirds of the human protein are similar to those of mouse, but are strikingly different from the corresponding domains in chicken. The evidence indicates that these erythroid regulatory factors evolved from a common precursor composed of two distinct kinds of repeated domains, which subsequently evolved at greatly different rates.