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
Chromatin regulators and transcriptional control of Drosophila development
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The development of a multicellular organism is programmed by complex patterns of gene expression. In eukaryotic cells, genes are packaged by histone proteins into chromatin. Chromatin regulators often function as transcription co-factors.

In this study, we have investigated the function of four co-factors, dAda2b, Reptin, Ebi and Brakeless during development of the fruit fly Drosophila melanogaster. dAda2b and Reptin belong to histone acetyl transferase (HAT) complexes, a SAGA-like complex and the Tip60 complex, respectively. We generated dAda2b mutants and found that lack of dAda2b strongly affects global histone acetylation and viability. We further propose that Ada2 may be involved in DNA repair. Our studies revealed new roles of Reptin and other Tip60 complex components in Polycomb Group mediated repression and heterochromatin formation, thereby promoting generation of silent chromatin.

During embryogenesis, transcriptional repressors establish localized and tissue-specific patterns of gene expression. In this thesis, we identified two novel co-repressors in the early embryo, Ebi and Brakeless. Ebi genetically and physically interacts with the Snail repressor. The Ebi-interaction motif in the Snail protein is essential for Snail function in vivo and is evolutionarily conserved in insects. We further demonstrated that Ebi associates with histone deacetylase 3 (HDAC3) and that histone deacetylation is part of the mechanism by which Snail mediates transcriptional repression.

We isolated Brakeless in a genetic screen for novel regulators of gene expression during embryogenesis. We found that mutation of brakeless impairs function of the Tailless repressor. Brakeless associates with Atrophin, another Tailless corepressor, and they function together in Tailless-mediated repression.

In summary, transcription co-factors, including chromatin regulators, are selectively required in distinct processes during development.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi , 2007. , 65 p.
Keyword [en]
Chromatin, Co-factors, Transcription, Development, Drosophila
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
URN: urn:nbn:se:su:diva-7209ISBN: 978-91-7155-547-2 (print)OAI: oai:DiVA.org:su-7209DiVA: diva2:197865
Public defence
2007-12-14, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 13:00
Opponent
Supervisors
Available from: 2007-11-22 Created: 2007-11-22Bibliographically approved
List of papers
1. Drosophila Ada2b is required for viability and normal histone H3 acetylation
Open this publication in new window or tab >>Drosophila Ada2b is required for viability and normal histone H3 acetylation
2004 In: Molelular and Cellular Biology, Vol. 24, 8080-8089 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24598 (URN)
Note
Part of urn:nbn:se:su:diva-7209Available from: 2007-11-22 Created: 2007-11-22Bibliographically approved
2. Drosophila Reptin and other TIP60 complex components pro-mote generation of silent chromatin
Open this publication in new window or tab >>Drosophila Reptin and other TIP60 complex components pro-mote generation of silent chromatin
2006 In: Genetics, Vol. 174, 241-251 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24599 (URN)
Note
Part of urn:nbn:se:su:diva-7209Available from: 2007-11-22 Created: 2007-11-22Bibliographically approved
3. Drosophila Ebi mediates Snail-dependent transcriptional repression through HDAC3-induced histone deacetylation
Open this publication in new window or tab >>Drosophila Ebi mediates Snail-dependent transcriptional repression through HDAC3-induced histone deacetylation
Show others...
2008 (English)In: EMBO Journal, ISSN 0261-4189, Vol. 27, no 6, 898-909 p.Article in journal (Refereed) Published
Abstract [en]

The Drosophila Snail protein is a transcriptional repressor that is necessary for mesoderm formation. Here, we identify the Ebi protein as an essential Snail co-repressor. In ebi mutant embryos, Snail target genes are derepressed in the presumptive mesoderm. Ebi and Snail interact both genetically and physically. We identify a Snail domain that is sufficient for Ebi binding, and which functions independently of another Snail co-repressor, Drosophila CtBP. This Ebi interaction domain is conserved among all insect Snail-related proteins, is a potent repression domain and is required for Snail function in transgenic embryos. In mammalian cells, the Ebi homologue TBL1 is part of the NCoR/SMRT–HDAC3 (histone deacetylase 3) co-repressor complex. We found that Ebi interacts with Drosophila HDAC3, and that HDAC3 knockdown or addition of a HDAC inhibitor impairs Snail-mediated repression in cells. In the early embryo, Ebi is recruited to a Snail target gene in a Snail-dependent manner, which coincides with histone hypoacetylation. Our results demonstrate that Snail requires the combined activities of Ebi and CtBP, and indicate that histone deacetylation is a repression mechanism in early Drosophila development.

Keyword
ChIP, chromatin, co-repressor, Drosophila development, transcription
Identifiers
urn:nbn:se:su:diva-24600 (URN)10.1038/emboj.2008.26 (DOI)000254179200008 ()
Note
Part of urn:nbn:se:su:diva-7209Available from: 2007-11-22 Created: 2007-11-22 Last updated: 2010-01-17Bibliographically approved
4. 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 In: Plos Biology, Vol. 5, 1298-1308 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24601 (URN)000247173200014 ()
Note
Part of urn:nbn:se:su:diva-7209Available from: 2007-11-22 Created: 2007-11-22Bibliographically approved

Open Access in DiVA

fulltext(865 kB)1377 downloads
File information
File name FULLTEXT01.pdfFile size 865 kBChecksum SHA-1
980300ab14c7ae9e36780eb3bdb465e6f73700a9fa96257c081f7a4056c9ad97f4a6bf1f
Type fulltextMimetype application/pdf

By organisation
Wenner-Gren Institute for Experimental Biology
Developmental Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 1377 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 518 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