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*
Graduate Group of Molecular Biology and
Laboratories of Biochemistry, Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
Transcription of the Ig 
light chain gene is controlled in part
by the 3' enhancer. Two of the proteins that bind to the 3'
enhancer, PU.1 and Pip, show tissue-restricted expression and may be
responsible for the tissue specificity of 3' enhancer activity. PU.1
alone can bind to DNA; however, Pip cannot bind to its 3' enhancer site
in electrophoretic mobility shift assays, unless recruited by PU.1.
Previously, we showed that the PU.1 PEST domain (rich in the amino
acids proline, glutamate, serine, and threonine; sequences 118–160) is
necessary for Pip recruitment to DNA. Here we used detailed mutagenic
analyzes of PU.1 to more precisely identify sequences required for Pip
recruitment by electrophoretic mobility shift assay. We found that
mutation of three segments within the PU.1 PEST domain (118–125,
133–139, and 141–147) modulated the efficiency of Pip recruitment,
while mutation of sequences between residues 88–118 and 154–168 had
no effect. Interestingly, we found that the PU.1 ETS domain (residues
170 to 255) is both necessary and sufficient for Pip interaction in
solution and that other ETS domain proteins can physically interact
with Pip as well. Our results suggest that Pip recruitment to DNA by
PU.1 occurs via a two-step mechanism. First, a physical interaction
that is not sufficient to recruit Pip occurs via the PU.1 ETS domain.
Second, a conformational change in the PU.1 PEST domain, apparently
mediated by serine phosphorylation, induces a conformational change in
Pip enabling it to bind to DNA. We also show that the PU.1 PEST domain
does not target PU.1 for rapid turnover.
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