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Mol. Cell. Biol., Dec 1995, 7091-7097, Vol 15, No. 12
B Peers, S Sharma, T Johnson, M Kamps and M Monteminy
A number of homeodomain proteins have been shown to regulate cellular
development by stimulating the transcription of specific target genes. In
contrast to their distinct activities in vivo, however, most homeodomain
proteins bind indiscriminately to potential target sites in vitro,
suggesting the involvement of cofactors which specify target site
selection. One such cofactor, termed extradenticle, has been shown to
influence segmental morphogenesis in Drosophila melanogaster by binding
cooperatively with certain homeodomain proteins to target regulatory
elements. Here we demonstrate that STF-1, an orphan homeodomain protein
required for pancreatic development in mammals, binds cooperatively to DNA
with Pbx, the mammalian homolog of extradenticle. Cooperative binding with
Pbx requires a pentapeptide motif (FPWMK) which is well conserved among a
large subset of homeodomain proteins. The FPMWK motif is not sufficient to
confer Pbx cooperativity on other homeodomain proteins, however; the
N-terminal arm of the STF-1 homeodomain is also essential. As cooperative
binding with Pbx occurs on only a subset of potential STF-1 target sites,
our results suggest that Pbx may specify target gene selection in the
developing pancreas by forming heterodimeric complexes with STF-1.
Copyright © 1995, American Society for Microbiology
The pancreatic islet factor STF-1 binds cooperatively with Pbx to a regulatory element in the somatostatin promoter: importance of the FPWMK motif and of the homeodomain
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037, USA.
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