E1B-AP5 was initially identified as a target of the early adenovirus E1B-55kDa protein during the course of lytic infection. E1B-AP5 belongs to the heterogeneous nuclear ribonucleoprotein family and was demonstrated to be involved in mRNA processing and transport [Gabler, Schutt, Groitl, Wolf, Shenk and Dobner (1998) J. Virol. 72, 7960–7971]. In the present paper, we demonstrate that E1B-AP5 differentially regulates basic and ligand-dependent transcription. We found that E1B-AP5 represses basic transcription driven by several virus and cellular promoters, and mapped the repression activity to the N-terminal part of the protein. In contrast with basic repression, E1B-AP5 activated the glucocorticoid-dependent promoter in the absence of dexamethasone, but did not contribute to the dexamethasone-induced activation. Mutant analysis indicated the presence of an additional cellular factor that modulates E1B-AP5 transcriptional activity. Using yeast two-hybrid screening, we identified a novel chromatin-associated bromodomain-containing protein, BRD7, as an E1B-AP5 interaction partner. We confirmed E1B-AP5–BRD7 complex formation in vivo and in vitro. We found that, although BRD7 binds to histones H2A, H2B, H3 and H4 through its bromodomain, this domain was not necessary for the interaction with E1B-AP5. Indeed, the triple complex formation of E1B-AP5, BRD7 and histones was demonstrated. Disruption of the E1B-AP5–BRD7 complex increased E1B-AP5 repression activity for basic transcription and converted it from being an activator of the hormone-dependent promoter into being a strong repressor. We conclude that complex formation between BRD7 and E1B-AP5 links chromatin events with mRNA processing at the level of transcriptional regulation.
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April 2003
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Research Article|
April 15 2003
Regulation of transcription by the heterogeneous nuclear ribonucleoprotein E1B-AP5 is mediated by complex formation with the novel bromodomain-containing protein BRD7
Julia KZHYSHKOWSKA;
Julia KZHYSHKOWSKA
1
∗Universität Heidelberg, Uni-Klinikum Mannheim, Dermatologie, Theodor-Kutzer-Ufer 1–3, D-68167 Mannheim, Germany
†Institut für Medizinische, Mikrobiologie und Hygiene, Universität Regensburg, D-93053 Regensburg, Germany
1To whom correspondence should be addressed (e-mail julia.kzhyshkowska@haut.ma.uni-heidelberg.de).
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Andre RUSCH;
Andre RUSCH
†Institut für Medizinische, Mikrobiologie und Hygiene, Universität Regensburg, D-93053 Regensburg, Germany
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Hans WOLF;
Hans WOLF
†Institut für Medizinische, Mikrobiologie und Hygiene, Universität Regensburg, D-93053 Regensburg, Germany
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Thomas DOBNER
Thomas DOBNER
†Institut für Medizinische, Mikrobiologie und Hygiene, Universität Regensburg, D-93053 Regensburg, Germany
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Publisher: Portland Press Ltd
Received:
August 13 2002
Revision Received:
December 09 2002
Accepted:
December 18 2002
Accepted Manuscript online:
December 18 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (2): 385–393.
Article history
Received:
August 13 2002
Revision Received:
December 09 2002
Accepted:
December 18 2002
Accepted Manuscript online:
December 18 2002
Citation
Julia KZHYSHKOWSKA, Andre RUSCH, Hans WOLF, Thomas DOBNER; Regulation of transcription by the heterogeneous nuclear ribonucleoprotein E1B-AP5 is mediated by complex formation with the novel bromodomain-containing protein BRD7. Biochem J 15 April 2003; 371 (2): 385–393. doi: https://doi.org/10.1042/bj20021281
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