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J Biol Chem, Vol. 274, Issue 7, 4067-4073, February 12, 1999
From the Laboratoire de Biologie Moléculaire et de
Génie Génétique, Institut de Chimie, Batiment B6,
Université de Liège, B-4000 Sart-Tilman, Belgium
Expression of the somatostatin gene in endocrine
pancreatic cells is controlled by several regulatory
cis-elements located in the promoter region. Among these,
the adjacent UE-A and TSEI elements, located from
Functional and Cooperative Interactions between the Homeodomain
PDX1, Pbx, and Prep1 Factors on the Somatostatin Promoter
113 to
85 relative to the transcription initiation site, function in
combination and act as a pancreas-specific mini-enhancer. The
TSEI element is recognized by the pancreatic homeodomain
factor PDX1. In the present study, we show that the UE-A element binds
a heterodimeric complex composed of a Pbx factor and the Prep1 protein,
both belonging to the atypical three-amino acid loop extension
homeodomain family. Recombinant Pbx1 and Prep1 proteins bind
cooperatively to the UE-A site, whereas neither protein can bind this
site alone. Transient transfection experiments reveal that both Pbx1
and Prep1 are required to generate a strong transcriptional activation
from the UE-A element when this element is inserted close to the TATA
box. In contrast, in the context of the intact somatostatin promoter or
mini-enhancer, Pbx1 and Prep1 alone have no effect, but they produce a
drastic activation when the pancreatic homeodomain factor PDX1 is also
coexpressed. Thus, the activity of the somatostatin mini-enhancer is
mediated by a cooperative interaction between the Pbx-Prep1
heterodimeric complex and the pancreatic factor PDX1.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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