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Molecular and Cellular Biology, March 2006, p. 2347-2359, Vol. 26, No. 6
0270-7306/06/$08.00+0 doi:10.1128/MCB.26.6.2347-2359.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, Missouri 63104,1 Department of Genetics, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri 631082
Received 22 November 2005/ Returned for modification 13 December 2005/ Accepted 24 December 2005
The Notch receptor controls development by activating transcription of specific target genes in response to extracellular signals. The factors that control assembly of the Notch activator complex on target genes and its ability to activate transcription are not fully known. Here we show, through genetic and molecular analysis, that the Drosophila Nipped-A protein is required for activity of Notch and its coactivator protein, mastermind, during wing development. Nipped-A and mastermind also colocalize extensively on salivary gland polytene chromosomes, and reducing Nipped-A activity decreases mastermind binding. Nipped-A is the fly homologue of the yeast Tra1 and human TRRAP proteins and is a key component of both the SAGA and Tip60 (NuA4) chromatin-modifying complexes. We find that, like Nipped-A, the Ada2b component of SAGA and the domino subunit of Tip60 are also required for mastermind function during wing development. Based on these results, we propose that Nipped-A, through the action of the SAGA and Tip60 complexes, facilitates assembly of the Notch activator complex and target gene transcription.
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