Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Functions of Transcriptional Co-regulators in Drosophila development
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
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 [en]
Transcription, Co-regulator, Development, Drosophila
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
URN: urn:nbn:se:su:diva-6817ISBN: 978-91-7155-436-9 (print)OAI: oai:DiVA.org:su-6817DiVA: diva2:197107
Public defence
2007-06-14, De Geersalen, Geovetenskapens hus, Svante Arrhenius väg 8 A, Stockholm, 10:00
Opponent
Supervisors
Available from: 2007-05-24 Created: 2007-05-02Bibliographically approved
List of papers
1. The CBP coactivator functions both upstream and downstream of Dpp/Screw signalling in the early Drosophila embryo
Open this publication in new window or tab >>The CBP coactivator functions both upstream and downstream of Dpp/Screw signalling in the early Drosophila embryo
2003 In: Developmental Biology, ISSN 0012-1606, Vol. 262, no 2, 294-302 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24250 (URN)
Note
Part of urn:nbn:se:su:diva-6817Available from: 2007-05-24 Created: 2007-05-02Bibliographically approved
2. The acetyltransferase activity of Drosophila CBP is dispensable for regulation of the Dpp pathway in the early embryo
Open this publication in new window or tab >>The acetyltransferase activity of Drosophila CBP is dispensable for regulation of the Dpp pathway in the early embryo
Show others...
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.

Keyword
Transcriptional control, Histone acetylation, TGF-beta signaling, Drosophla embryo development
National Category
Developmental Biology
Identifiers
urn:nbn:se:su:diva-24251 (URN)10.1016/j.ydbio.2007.01.036 (DOI)
Available from: 2007-05-24 Created: 2007-05-02 Last updated: 2017-12-13Bibliographically approved
3. Drosophila Brakeless interacts with Atrophin and is required for Tailless-mediated transcriptional repression in early embryos
Open this publication in new window or tab >>Drosophila Brakeless interacts with Atrophin and is required for Tailless-mediated transcriptional repression in early embryos
Show others...
2007 (English)In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 5, no 6Article in journal (Refereed) Published
Abstract [en]

Complex gene expression patterns in animal development are generated by the interplay of transcriptional activators and repressors at cis-regulatory DNA modules (CRMs). How repressors work is not well understood, but often involves interactions with co-repressors. We isolated mutations in the brakeless gene in a screen for maternal factors affecting segmentation of the Drosophila embryo. Brakeless, also known as Scribbler, or Master of thickveins, is a nuclear protein of unknown function. In brakeless embryos, we noted an expanded expression pattern of the Krüppel (Kr) and knirps (kni) genes. We found that Tailless-mediated repression of kni expression is impaired in brakeless mutants. Tailless and Brakeless bind each other in vitro and interact genetically. Brakeless is recruited to the Kr and kni CRMs, and represses transcription when tethered to DNA. This suggests that Brakeless is a novel co-repressor. Orphan nuclear receptors of the Tailless type also interact with Atrophin co-repressors. We show that both Drosophila and human Brakeless and Atrophin interact in vitro, and propose that they act together as a co-repressor complex in many developmental contexts. We discuss the possibility that human Brakeless homologs may influence the toxicity of polyglutamine-expanded Atrophin-1, which causes the human neurodegenerative disease dentatorubral-pallidoluysian atrophy (DRPLA).

Place, publisher, year, edition, pages
Haecker et al, 2007
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-24252 (URN)10.1371/journal.pbio.0050145 (DOI)
Note
Part of urn:nbn:se:su:diva-6817Available from: 2007-05-24 Created: 2007-05-02 Last updated: 2017-12-13Bibliographically approved
4. Drosophila Reptin and other TIP60 complex components promote generation of silent chromatin
Open this publication in new window or tab >>Drosophila Reptin and other TIP60 complex components promote generation of silent chromatin
2006 In: Genetics, ISSN 0016-6731, Vol. 174, 241-251 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24253 (URN)
Note
Part of urn:nbn:se:su:diva-6817Available from: 2007-05-24 Created: 2007-05-02Bibliographically approved

Open Access in DiVA

No full text

By organisation
Wenner-Gren Institute for Experimental Biology
Developmental Biology

Search outside of DiVA

GoogleGoogle Scholar

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 206 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf