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Vol. 12, No. 18, pp. 2863-2873, September 15, 1998
-globin locus control region in vivo
Erasmus University Rotterdam, Medical Genetics Center-Department of
Cell Biology, 3000 DR Rotterdam, The Netherlands
The locus control region of the 
-globin
cluster contains five DNase I hypersensitive sites (5'HS1-5)
required for locus activation. 5'HS3 contains six G-rich motifs
that are essential for its activity. Members of a protein family,
characterized by three zinc fingers highly homologous to those found in
transcription factor Sp1, interact with these 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 the zinc fingers of
Sp1 and EKLF. Testing their activity in transgenic mice shows that EKLF
is a direct activator of 5'HS3.
[Key Words: Zinc fingers; binding site specificity; locus control region; Sp1; EKLF; transcriptional activation; globin]
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