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First published online 19 April 2006
doi: 10.1242/dev.02372
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1 Program in Developmental Biology, Baylor College of Medicine, Houston, TX
77030, USA.
2 Department of Molecular and Human Genetics, Baylor College of Medicine,
Houston, TX 77030, USA.
3 Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX
77030, USA.
4 Institute of Molecular Biology and Biotechnology, FORTH and Department of
Biology, University of Crete, Heraklion, GR-71110, Greece.
Author for correspondence (e-mail:
hbellen{at}bcm.tmc.edu)
Accepted 20 March 2006
The zinc-finger transcription factor Senseless is co-expressed with basic
helix-loop-helix (bHLH) proneural proteins in Drosophila sensory
organ precursors and is required for their normal development. High levels of
Senseless synergize with bHLH proteins and upregulate target gene expression,
whereas low levels of Senseless act as a repressor in vivo. However, the
molecular mechanism for this dual role is unknown. Here, we show that
Senseless binds bHLH proneural proteins via its core zinc fingers and is
recruited by proneural proteins to their target enhancers to function as a
co-activator. Some point mutations in the Senseless zinc-finger region abolish
its DNA-binding ability but partially spare the ability of Senseless to
synergize with proneural proteins and to induce sensory organ formation in
vivo. Therefore, we propose that the structural basis for the switch between
the repressor and co-activator functions of Senseless is the ability of its
core zinc fingers to interact physically with both DNA and bHLH proneural
proteins. As Senseless zinc fingers are 
90% identical to the
corresponding zinc fingers of its vertebrate homologue Gfi1, which is thought
to cooperate with bHLH proteins in several contexts, the Senseless/bHLH
interaction might be evolutionarily conserved.
Key words: Drosophila, Senseless
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