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Molecular and Cellular Biology, December 2000, p. 9317-9330, Vol. 20, No. 24
Vollum Institute and Department of Cell and
Developmental Biology, Oregon Health Sciences University, Portland,
Oregon 97201
Received 15 June 2000/Returned for modification 24 July
2000/Accepted 19 September 2000
CREB-binding protein (CBP) is a coactivator for multiple
transcription factors that transduce a variety of signaling pathways. Current models propose that CBP enhances gene expression by bridging the signal-responsive transcription factors with components of the
basal transcriptional machinery and by augmenting the access of
transcription factors to DNA through the acetylation of histones. To
define the pathways and proteins that require CBP function in a living
organism, we have begun a genetic analysis of CBP in flies. We have
overproduced Drosophila melanogaster CBP (dCBP) in a
variety of cell types and obtained distinct adult phenotypes. We used
an uninflated-wing phenotype, caused by the overexpression of dCBP in
specific central nervous system cells, to screen for suppressors of
dCBP overactivity. Two genes with mutant versions that act as dominant
suppressors of the wing phenotype were identified: the
PKA-C1/DCO gene, encoding the catalytic subunit of cyclic AMP protein kinase, and ash1, a member of the
trithorax group (trxG) of chromatin modifiers.
Using immunocolocalization, we showed that the ASH1 protein is
specifically expressed in the majority of the dCBP-overexpressing
cells, suggesting that these proteins have the potential to interact
biochemically. This model was confirmed by the findings that the
proteins interact strongly in vitro and colocalize at specific sites on
polytene chromosomes. The trxG proteins are thought to maintain gene
expression during development by creating domains of open chromatin
structure. Our results thus implicate a second class of
chromatin-associated proteins in mediating dCBP function and imply that
dCBP might be involved in the regulation of higher-order chromatin structure.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Functional Interaction between the Coactivator
Drosophila CREB-Binding Protein and ASH1, a Member of
the Trithorax Group of Chromatin Modifiers

*
Corresponding author. Mailing address: Department of
Cell and Developmental Biology L-215, Oregon Health Sciences
University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201. Phone:
(503) 494-7192. Fax: (503) 494-4353. E-mail: smoliks{at}ohsu.edu.
Present address: Institut de Génétique Humaine,
CNRS UPR1142, Montpellier, France.
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