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Molecular and Cellular Biology, August 2005, p. 6559-6569, Vol. 25, No. 15
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.15.6559-6569.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human SRCAP and Drosophila melanogaster DOM Are Homologs That Function in the Notch Signaling Pathway{dagger}

Joel C. Eissenberg,1* Madeline Wong,2 and John C. Chrivia2

Edward A. Doisy Department of Biochemistry and Molecular Biology,1 Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 631042

Received 26 February 2005/ Returned for modification 26 March 2005/ Accepted 11 May 2005

The putative ATPase chromatin-remodeling machine SRCAP was identified in a yeast two-hybrid protein screen by interaction with the histone acetylase CBP. SRCAP is implicated in the transcriptional coactivation of cyclic AMP- and steroid-dependent promoters, but no natural chromosomal targets for SRCAP regulation have been identified. DOM is the unique SRCAP homolog in Drosophila melanogaster. The goal of this study was to test whether SRCAP is a functional homolog of DOM and to identify potential activities and targets of SRCAP in vivo. We show that human SRCAP complements recessive domino mutant phenotypes. This rescue depends on an intact ATPase homology domain. SRCAP colocalizes extensively with DOM on Drosophila polytene chromosomes and is recruited to sites of active transcription, such as steroid-regulated loci, but not to activated heat shock loci. We show that SRCAP recruits Drosophila CBP to ectopic chromosomal sites, providing the first evidence to suggest that SRCAP and CBP interact directly or indirectly on chromosomes. We show that DOM is a Notch pathway activator in Drosophila and that wild-type SRCAP—but not an ATPase domain mutant—can substitute for DOM in Notch-dependent wing development. We show that SRCAP potentiates Notch-dependent gene activation in HeLa cells. Taken together, these data implicate SRCAP and DOM in developmental gene activation.

* Corresponding author. Mailing address: Saint Louis University School of Medicine, Edward A. Doisy Dept. of Biochemistry and Molecular Biology, 221 N. Grand Blvd., St. Louis, MO 63101. Phone: (314) 977-9235. Fax: (314) 977-9205. E-mail: eissenjc{at}slu.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, August 2005, p. 6559-6569, Vol. 25, No. 15
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.15.6559-6569.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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