The Acetyltransferase Activity of CBP Is Required for wingless Activation and H4 Acetylation in Drosophila melanogaster

Abstract

CBP is a critical coactivator of transcription, but little is understood about the importance of its intrinsic acetyltransferase (AT) activity in gene activation in vivo. We show that the intrinsic AT function of CBP in Drosophila melanogaster (dCBP) is necessary to maintain a dCBP overexpression phenotype in the eye, for the in vivo activation of a specific target gene, wingless, and for the global acetylation of histone H4. These findings indicate that a point mutation which alters the intrinsic AT activity of CBP (only one of many CBP functions) has profound effects on CBP-induced gene activation in a physiologically intact transcription system. Furthermore, the effects of CBP AT activity are not limited to a few specific promoters, but rather CBT AT activity may play a role in regulating global histone acetylation throughout the developing organism.

We thank J. Notis, B. Newman, and J.-R. Cardinaux for their technical advice; A. Snyder (MMI, OHSU, and the Oregon Hearing Research Center) for her technical assistance with confocal microscopy; and W. Wolfgang, M. Webb, and Edwin Florance (Lewis and Clark College) for their assistance with histology and SEM.

This work was supported in part by awards from the NIH, the Endocrine Fellows Foundation, and the Medical Research Foundation of Oregon.