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Regulation of the Drosophila engrailed gene by Polycomb repressor complex 2
Umeå University, Faculty of Medicine, Molecular Biology. (Åsa Rasmuson-Lestander)
Umeå University, Faculty of Medicine, Molecular Biology. (Åsa Rasmunso-Lestander)
2009 (English)In: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 126, no 5-6, 443-448 p.Article in journal (Refereed) Published
Abstract [en]

Suppressor-of-zeste-12 (Su(z)12) is a core component of the Polycomb repressive complex 2 (PRC2), which has a methyltransferase activity directed towards lysine residues of histone 3. Mutations in Polycomb group (PcG) genes cause de-repression of homeotic genes and subsequent homeotic transformations. Another target for Polycomb silencing is the engrailed gene, which encodes a key regulator of segmentation in the early Drosophila embryo. In close proximity to the en gene is a Polycomb Response Element, but whether en is regulated by Su(z)12 is not known. In this report, we show that en is not de-repressed in Su(z)12 or Enhancer-of-zeste mutant clones in the anterior compartment of wing discs. Instead, we find that en expression is down-regulated in the posterior portion of wing discs, indicating that the PRC2 complex acts as an activator of en. Our results indicate that this is due to secondary effects, probably caused by ectopic expression of Ubx and Abd-B.

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2009. Vol. 126, no 5-6, 443-448 p.
Keyword [en]
Gene regulation, Su(z)12, Engrailed, Wing disc, Drosophila
National Category
Cell and Molecular Biology Developmental Biology
URN: urn:nbn:se:umu:diva-18646DOI: 10.1016/j.mod.2009.01.004ISI: 000266975100014OAI: diva2:174303
Available from: 2009-02-20 Created: 2009-02-20 Last updated: 2016-08-31Bibliographically approved
In thesis
1. Expression and function of Suppressor of zeste 12 in Drosophila melanogaster
Open this publication in new window or tab >>Expression and function of Suppressor of zeste 12 in Drosophila melanogaster
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The development of animals and plants needs a higher order of regulation of gene expression to maintain proper cell state. The mechanisms that control what, when and where a gene should (or should not) be expressed are essential for correct organism development. The Polycomb group (PcG) is a family of genes responsible for maintaining gene silencing and Suppressor of zeste 12 (Su(z)12) is one of the core components in the PcG. The gene is highly conserved in organisms ranging from plants to humans, however, the specific function is not well known. The main tasks of this thesis was to investigate the function of Su(z)12 and its expression at different stages of Drosophila development.

In polytene chromosomes of larval salivary glands, Su(z)12 binds to about 90 specific euchromatic sites. The binding along the chromosome arms is mostly in interbands, which are the most DNA de-condensed regions. The binding sites of Su(z)12 in polytene chromosomes correlate precisely with those of the Enhancer-of-zeste (E(z)) protein, indicating that Su(z)12 mainly exists within the Polycomb Repressive Complex 2 (PRC2). However, the binding pattern does not overlap well with Histone 3 lysine 27 tri-methylations (H3K27me3), the specific chromatin mark created by PRC2. The Su(z)12 binding to chromatin is dynamically regulated during mitotic and meiotic cell division. The two different Su(z)12 isoforms: Su(z)12-A and Su(z)12-B (resulting from alternative RNA splicing), have very different expression patterns during development. Functional analyses indicate that they also have different functions he Su(z)12-B form is the main mediator of silencing. Furthermore, a neuron specific localization pattern in larval brain and a giant larval phenotype in transgenic lines reveal a potential function of Su(z)12-A in neuron development.  In some aspects the isoforms seem to be able to substitute for each other.

The histone methyltransferase activity of PRC2 is due to the E(z) protein. However, Su(z)12 is also necessary for H3K27me3 methylation in vivo, and it is thus a core component of PRC2. Clonal over-expression of Su(z)12 in imaginal wing discs results in an increased H3K27me3 activity, indicating that Su(z)12 is a limiting factor for silencing. When PcG function is lost, target genes normally become de-repressed. The segment polarity gene engrailed, encoding a transcription factor, is a target for PRC2 silencing. However, we found that it was not activated when PRC2 function was deleted. We show that the Ultrabithorax protein, encoded by another PcG target gene, also acts as an inhibitor of engrailed and that de-regulation of this gene causes a continued repression of engrailed. The conclusion is that a gene can have several negative regulators working in parallel and that secondary effects have to be taken into consideration, when analyzing effects of mutants.

PcG silencing affects very many cellular processes and a large quantity of knowledge is gathered on the overall mechanisms of PcG regulation. However, little is known about how individual genes are silenced and how cells “remember” their fate through cell generations.

Place, publisher, year, edition, pages
Umeå University: , 2009. 92 p.
Epigenetics, histone, polycomb, Drosophila, Suppressor of zeste 12
National Category
Research subject
urn:nbn:se:umu:diva-18483 (URN)978-91-7264-729-9 (ISBN)
Public defence
2009-03-06, Major Groove, , Molecular Biology Department, Umeå University, Byggnad 6L, 10:00 (English)
Available from: 2009-02-13 Created: 2009-02-10 Last updated: 2009-02-20Bibliographically approved

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