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J. Biol. Chem., Vol. 280, Issue 2, 1299-1305, January 14, 2005

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Role of the Sc C Terminus in Transcriptional Activation and E(spl) Repressor Recruitment^*

Nikolaos Giagtzoglou¶, Konstantinos A. Koumbanakis, John Fullard||, Ioanna Zarifi, and Christos Delidakis**

From the Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Vasilika Vouton, Heraklion, GR 71110, Greece and the Department of Biology, University of Crete, Heraklion, GR 71110, Greece

Neurogenesis in all animals is triggered by the activity of a group of basic helix-loop-helix transcription factors, the proneural proteins, whose expression endows ectodermal regions with neural potential. The eventual commitment to a neural precursor fate involves the interplay of these proneural transcriptional activators with a number of other transcription factors that fine tune transcriptional responses at target genes. Most prominent among the factors antagonizing proneural protein activity are the HES basic helix-loop-helix proteins. We have previously shown (1) that two HES proteins of Drosophila, E(spl)m and E(spl)m7, interact with the proneural protein Sc and thereby get recruited onto Sc target genes to repress transcription. Using in vivo and in vitro assays we have now discovered an important dual role for the Sc C-terminal domain. On one hand it acts as a transcription activation domain, and on the other it is used to recruit E(spl) proteins. In vivo, the Sc C-terminal domain is required for E(spl) recruitment in an enhancer context-dependent fashion, suggesting that in some enhancers alternative interaction surfaces can be used to recruit E(spl) proteins.

Received for publication, August 5, 2004 , and in revised form, October 19, 2004.

^* This work was supported by the PENED Grants 99ED185 and 2001–1ED207 from the General Secretariat of Research and Technology of Greece, as well as by intramural Institute of Molecular Biology and Biotechnology funds. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental text and figures.

^¶ Recipient of a Greek State (IKY) Scholarship.

^|| Supported by European Union Marie Curie Host Fellowship Contract HPMD-CT-2001–00096.

^** To whom correspondence should be addressed: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Vasilika Vouton, Heraklion, GR 71110, Greece. Tel.: 30-2810-391-112; Fax: 30-2810-391-104; E-mail: delidaki{at}imbb.forth.gr.

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