N. Gillemans et al., ALTERED DNA-BINDING SPECIFICITY MUTANTS OF EKLF AND SP1 SHOW THAT EKLF IS AN ACTIVATOR OF THE BETA-GLOBIN LOCUS-CONTROL REGION IN-VIVO, Genes & development, 12(18), 1998, pp. 2863-2873
The locus control region of the beta-globin cluster contains five DNas
e I hypersensitive sites (5'HS1-5) required for locus activation. 5'HS
3 contains six G-rich motifs that are essential for its activity. Memb
ers of a protein family, characterized by three zinc fingers highly ho
mologous to those found in transcription factor Sp1, interact with the
se motifs. Because point mutagenesis cannot distinguish between family
members, it is not known which protein activates 5'HS3. We show that
the function of such closely related proteins can be distinguished in
vivo by matching point mutations in 5'HS3 with amino acid changes in t
he zinc fingers of Sp1 and EKLF. Testing their activity in transgenic
mice shows that EKLF is a direct activator of 5'HS3.