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Development 130 (2): 259-270

Two modes of recruitment of E(spl) repressors onto target genes

Nikolaos Giagtzoglou1,2, Pavlos Alifragis1,2,*, Konstantinos A. Koumbanakis1,2, and Christos Delidakis1,2,{dagger}

1 Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Heraklion, Greece
2 Department of Biology, University of Crete, Heraklion, Greece
* Present address: Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK

{dagger} Author for correspondence (e-mail: delidaki{at}imbb.forth.gr)

Accepted for publication 10 October 2002.

Abstract: The decision of ectodermal cells to adopt the sensory organ precursor fate in Drosophila is controlled by two classes of basic-helix-loop-helix transcription factors: the proneural Ac and Sc activators promote neural fate, whereas the E(spl) repressors suppress it. We show here that E(spl) proteins m7 and m{gamma} are potent inhibitors of neural fate, even in the presence of excess Sc activity and even when their DNA-binding basic domain has been inactivated. Furthermore, these E(spl) proteins can efficiently repress target genes that lack cognate DNA binding sites, as long as these genes are bound by Ac/Sc activators. This activity of E(spl)m7 and m{gamma} correlates with their ability to interact with proneural activators, through which they are probably tethered on target enhancers. Analysis of reporter genes and sensory organ (bristle) patterns reveals that, in addition to this indirect recruitment of E(spl) onto enhancers via protein-protein interaction with bound Ac/Sc factors, direct DNA binding of target genes by E(spl) also takes place. Irrespective of whether E(spl) are recruited via direct DNA binding or interaction with proneural proteins, the co-repressor Groucho is always needed for target gene repression.

Key Words: Basic-helix-loop-helix • Proneural • HES • Transcriptional repression • Neurogenesis • Lateral inhibition • Drosophila • E(spl)

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