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Mol. Cell. Biol. doi:10.1128/MCB.00421-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Co-repressor CtBP and nuclear speckle protein Pnn/DRS differentially modulate transcription and splicing of the E-cadherin gene

Department of Anatomy and Cell Biology, Department of Biochemistry, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, Florida 32610, USA; Division of Endocrinology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115, USA

^* To whom correspondence should be addressed. Email: Sugrue{at}anatomy.med.ufl.edu.

	Abstract

CtBP is a transcriptional co-repressor with tumorgenic potential, that targets the promoter of the tumor suppressor gene E-cadherin. Pnn/DRS (Pnn) is a "nuclear speckle"-associated protein involved in mRNA processing as well as transcriptional regulation of E-cadherin via its binding to CtBP. Here, we show that CtBP can recruit Pnn to CtBP-associated complexes, resulting in the Pnn-dependent chromatin remodeling at the E-cadherin promoter. In addition, CtBP and Pnn can differentially modulate E-cadherin mRNA splicing with Pol II serving as an interface in this event. Therefore, the Pnn/CtBP functional interplay represents a novel mechanism linking the co-repressor CtBP and Pnn to the transcription-coupled mRNA splicing of a major tumor suppressor gene. Our findings implicate the existence of the molecular switches involved in tumorgenesis, which coordinate promoter specific events and mRNA processing, by serving as bridging elements between the regulatory complexes both at gene promoters and within the mRNA splicing machineries.