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The acetyltransferase activity of Drosophila CBP is dispensable for regulation of the Dpp pathway in the early embryo
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
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2007 (English)In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 305, no 2, 650-658 p.Article in journal (Refereed) Published
Abstract [en]

The CBP protein is a transcriptional co-activator and histone acetyltransferase. Reduced expression of Drosophila CBP (dCBP) in the early embryo specifically impairs signaling by the TGF-β molecules Dpp and Screw (Scw). This occurs by a failure to activate transcription of the tolloid (tld) gene, which codes for a protease that generates active Dpp and Scw ligands. We show that dCBP directly regulates this gene by binding to the tld enhancer, and that tld expression can be partially rescued with a dCBP transgene. At a slightly later stage of development, Dpp/Scw signaling recovers in mutant embryos, but is unable to turn on expression of the Dpp/Scw-target gene rhomboid (rho). Interestingly, an acetyltransferase (AT)-defective dCBP transgene rescued tld and rho gene expression to an extent comparable to the wild-type transgene, whereas a transgene containing a 130 amino acid deletion rescued tld but not late rho expression. A tracheal phenotype caused by the reduced dCBP levels was also rescued more efficiently with the wild-type dCBP transgene than with this mutant transgene. Our results indicate that separate parts of the dCBP protein are required on different promoters, and that the AT activity of dCBP is dispensable for certain aspects of Dpp signaling. We discuss the similarity of these results to the role of p300/CBP in TGF-β signaling in the mouse.

Place, publisher, year, edition, pages
2007. Vol. 305, no 2, 650-658 p.
Keyword [en]
Transcriptional control, Histone acetylation, TGF-beta signaling, Drosophla embryo development
National Category
Developmental Biology
Identifiers
URN: urn:nbn:se:su:diva-24251DOI: 10.1016/j.ydbio.2007.01.036OAI: oai:DiVA.org:su-24251DiVA: diva2:197104
Available from: 2007-05-24 Created: 2007-05-02 Last updated: 2011-05-23Bibliographically approved
In thesis
1. Functions of Transcriptional Co-regulators in Drosophila development
Open this publication in new window or tab >>Functions of Transcriptional Co-regulators in Drosophila development
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During Drosophila development, regulation of gene expression through interplay between transcriptional activators and repressors is generating complex patterns of gene expression that leads to cell differentiation. For proper control of transcription, transcription factors bind to DNA at control regions, so called Cis Regulatory Modules (CRM). Transcription factors recruit additional factors, co-regulators, that affect gene expression through interactions with the general transcription machinery, as well as affect the chromatin environment through post-translational modifications of the histone tails. In this thesis the role of transcriptional co-regulators in Drosophila development is investigated.

This work has demonstrated the need for the transcriptional co-activator CREB binding protein (CBP) in signalling by the Transforming Growth Factor-β (TGF-β) molecules Decapentaplegic (Dpp) and Screw (Scw) in early embryos. Furthermore it is shown that the acetyl transferase activity of CBP is dispensable for this function.

In a screen for novel regulators of gene expression in the embryo, Brakeless (Bks) was isolated as a co-repressor for the Tailless (Tll) transcription factor. This work shows that Tll function is impaired in bks mutants, that Bks and Tll bind each other in vitro and interact genetically. Bks is present on CRMs controlled by Tll and can repress transcription when tethered to DNA. Bks interacts and functions together with another co-repressor Atrophin.

Reptin is part of several complexes including the TIP60 Histone Acetyl Transferase (HAT) complex. Work in this thesis show that Reptin and other members of the TIP60 complex function in formation of silent chromatin in Drosophila.

Together these results show that transcriptional co-regulators function selectively in specific processes during development.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi, 2007. 75 p.
Keyword
Transcription, Co-regulator, Development, Drosophila
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
urn:nbn:se:su:diva-6817 (URN)978-91-7155-436-9 (ISBN)
Public defence
2007-06-14, De Geersalen, Geovetenskapens hus, Svante Arrhenius väg 8 A, Stockholm, 10:00
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Available from: 2007-05-24 Created: 2007-05-02Bibliographically approved

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