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J. Biol. Chem., Vol. 278, Issue 45, 43901-43909, November 7, 2003

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A Composite Motif of the Drosophila Morphogenetic Protein Bicoid Critical to Transcription Control^*

Chen Zhao, Dechen Fu, Vrushank Dave, and Jun Ma

From the Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229

Bicoid is a molecular morphogen-controlling embryonic patterning in Drosophila. It is a homeodomain-containing protein that activates specific target genes during early embryogenesis. Our recent studies have identified a domain of Bcd located outside its homeodomain and referred to as a self-inhibitory domain that can dramatically repress its own ability to activate transcription. Here we present evidence that the self-inhibitory function is evolutionarily conserved. A systematic analysis of this domain reveals a composite 10-amino acid motif with interdigitating residues that regulate Bcd activity in opposite manners. Mutations within the Bcd motif can exert their respective effects when the self-inhibitory domain is grafted to an entirely heterologous activator, but they do not affect DNA binding in vitro or subcellular localization of Bcd in cells. We further show that the self-inhibitory domain of Bcd can interact with Sin3A, a component of the histone deacetylase co-repressor complex. Our study suggests that the activity of Bcd is intricately controlled by multiple mechanisms involving the actions of co-repressor proteins.

Received for publication, March 17, 2003 , and in revised form, August 8, 2003.

^* This work was supported in part by grants from the National Institutes of Health, the American Heart Association, and the National Science Foundation (to J. M.). 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.

Current address: Institute of Cellular and Molecular Biology, University of Texas, Austin, TX 78712.

To whom correspondence should be addressed: Division of Developmental Biology, Children's Hospital Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229. Tel.: 513-636-7977; Fax: 513-636-4317; E-mail: jun.ma{at}cchmc.org.

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