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J. Biol. Chem., Vol. 275, Issue 36, 28157-28166, September 8, 2000
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,
From the Laboratory of Molecular Biology, NIDDKD, National
Institutes of Health, Bethesda, Maryland 20892
GATA-1 and other vertebrate GATA factors contain
a DNA binding domain composed of two adjacent homologous zinc fingers.
Whereas only the C-terminal finger of GATA-1 is capable of independent binding to the GATA recognition sequence, double GATA sites that require both fingers for high affinity interaction are found in several
genes. We propose a mechanism whereby adjacent zinc fingers interact to
influence the binding and transactivation properties of GATA-1 at a
subset of DNA-binding sites. By using two such double GATA sites we
demonstrate that the N-terminal finger and adjacent linker region can
alter the binding specificity of the C-terminal finger sufficiently to
prevent it from recognizing some consensus GATA sequences. Therefore,
the two zinc fingers form a composite binding domain having a different
DNA binding specificity from that shown by the constituent single
C-terminal finger. Furthermore, we compare two of these double sites
and show that high affinity binding of GATA-1 to a reporter gene does not necessarily induce transactivation, namely the sequence of the
DNA-binding site can alter the ability of GATA-1 to stimulate transcription.
To whom correspondence should be addressed. Tel.: 301-496-5889;
Fax: 301-496-0201; E-mail: ceceliat@intra.niddk.nih.gov.
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