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J. Biol. Chem., Vol. 276, Issue 21, 17985-17993, May 25, 2001
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From the Department of Molecular Biology, University of Texas
Southwestern Medical Center, Dallas, Texas 75390-9148
In pancreatic acinar cells, the HOX-like factor
PDX1 acts as part of a trimeric complex with two TALE class homeodomain
factors, PBX1b and MEIS2b. The complex binds to overlapping half-sites for PDX1 and PBX. The trimeric complex activates transcription in cells
to a level about an order of magnitude greater than PDX1 alone. The
N-terminal PDX1 activation domain is required for detectable transcriptional activity of the complex, even though PDX1 truncations bearing only the PDX1 C-terminal homeodomain and pentapeptide motifs
can still participate in forming the trimeric complex. The conserved
N-terminal PBC-B domain of PBX, as well as its homeodomain, is required
for both complex formation and transcriptional activity. Only the
N-terminal region of MEIS2, including the conserved MEIS domains, is
required for formation of a trimer on DNA and transcriptional activity:
the MEIS homeodomain is dispensable. The activity of the
pancreas-specific ELA1 enhancer requires the cooperation of the trimer-binding element and a nearby element that binds the pancreatic transcription factor PTF1. We show that the
PDX1· PBX1b·MEIS2b complex cooperates with the PTF1 basic
helix-loop-helix complex to activate an ELA1 minienhancer
in HeLa cells and that this cooperation requires all three homeoprotein
subunits, including the PDX1 activation domain.
DNA Binding and Transcriptional Activation by a
PDX1·PBX1b·MEIS2b Trimer and Cooperation with a
Pancreas-specific Basic Helix-Loop-Helix Complex*
*
This research was supported by Grant DK-55266 from the
National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Molecular
Biology, University of Texas Southwestern Medical Center, 5323 Harry
Hines Blvd., Dallas, TX 75390-9148. Tel.: 214-648-1942; Fax:
214-648-1915; E-mail: swift@hamon.swmed.edu.
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