The erythroid-specific transcription factor Eryfl binds to DNA sites within regulatory regions of every memberof both the a-and P-globin families in chicken. The distribution of these sites suggests, that Eryfl may serve as a general “switch” factor for erythroid development. We have cloned the cDNA for Eryfl and show that the corresponding mRNA is present in all erythroid lineages, but is absent from non-erythroid cells. We demonstrate that the cDNA encodes the specific Eryfl binding activity found in erythrocytes. Eryfl is a basic 38 kd protein containing a pair of highly similar “fingers” with the motif Cys-xx-Cys-x1,-Cys-xx-Cys. The amino acid sequences of these regions bear no resemblance to those found in other regulatory proteins with a similar arrangement of cysteine residues. Our evidence suggests, furthermore, that transition metal ions are unusually tightly bound, or may not be necessary for the sequence-specific DNA binding of Eryft.

The regulation of globin gene expression involves interactions between sequence-specific DNA binding factors and transcriptional regulatory regions (enhancers, promoters, or both) near each member of the globin family (Felsenfeld et al., 1989) as well as at distant loci within the chromatin loops containing these genes (Grosveld et al., 1987). These regulatory mechanisms are of course quite similar to those used by a variety of other genes: Most of the globin genes, particularly those of the 8 family, are controlled by combinations of relatively ubiquitous regulatory factors (Felsenfeld et al., 1989; Myers et al., 1986). Erythroid cells, however, contain erythroid-specific factors as well. We have recently described such a factor, Eryfl, which is found in chicken erythroid cells (Evans et al., 1988). The Eryfl binding site has the consensus sequence (A/T) GAT (ATT)(A/G); it was first identified in the promoters of the aD and p genes (Kemper et al., 1987), and its function as a strong positive regulatory element was demonstrated in the PA/& globin enhancer (Evans et al., 1988; R&man and Felsenfeld, 1988). Eryfl binding sites are found either in the promoter or en’hancer of each member of both the a-and 8-globin gene, families of chicken. Eryfl binding activity is present at high concentrations in erythroid cells at all stages of development, but is absent from all non-erythroid cells that