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Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster.
Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Science and Technology).
Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Science and Technology).
Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Science and Technology).
Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Science and Technology).
2007 (English)In: EMBO J, ISSN 0261-4189, Vol. 26, no 9, 2307-2316 p.Article in journal (Refereed) Published
Abstract [en]

Drosophila melanogaster exhibits two expression-regulating systems that target whole, specific chromosomes: the dosage compensation system whereby the male-specific lethal complex doubles transcription of genes on the male X-chromosome and the chromosome 4-specific protein Painting of fourth, POF. POF is the first example of an autosome-specific protein and its presence raises the question of the universality of chromosome-specific regulation. Here we show that POF and heterochromatin protein 1 (HP1) are involved in the global regulation of the 4th chromosome. Contrary to previous conclusions, Pof is not essential for survival of diplo-4th karyotype flies. However, Pof is essential for survival of haplo-4th individuals and expression of chromosome 4 genes in diplo-4th individuals is decreased in the absence of Pof. Mapping of POF using chromatin immunoprecipitation suggested that it binds within genes. Furthermore, we show that POF binding is dependent on heterochromatin and that POF and HP1 bind interdependently to the 4th chromosome. We propose a balancing mechanism involving POF and HP1 that provides a feedback system for fine-tuning expression status of genes on the 4th chromosome.

Place, publisher, year, edition, pages
2007. Vol. 26, no 9, 2307-2316 p.
Keyword [en]
Animals, Chromosomal Proteins; Non-Histone/genetics/*metabolism, Chromosomes/*genetics, Dosage Compensation; Genetic, Drosophila Proteins/genetics/*metabolism, Drosophila melanogaster/genetics/*physiology, Gene Expression Regulation, Heterochromatin/*physiology, Male
Identifiers
URN: urn:nbn:se:umu:diva-17029PubMedID: 17318176OAI: oai:DiVA.org:umu-17029DiVA: diva2:156702
Available from: 2008-01-12 Created: 2008-01-12 Last updated: 2012-04-11Bibliographically approved
In thesis
1. Chromosome-wide gene regulatory mechanisms in Drosophila melanogaster
Open this publication in new window or tab >>Chromosome-wide gene regulatory mechanisms in Drosophila melanogaster
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In Drosophila there are two different chromosome-wide targeting systems, the dosage compensation system that equalizes the transcriptional output from X-linked genes between males and females, and the regulation of the 4th chromosome mediated by the POF protein.

 

The best studied of these two mechanisms is the dosage compensation system. To attain dosage compensation in Drosophila at least five different proteins, encoded by the male-specific lethal genes msl1, msl2, msl3, mle and mof, are required. These proteins together with two non-coding RNAs (roX1 and roX2) form a dosage compensation complex (MSL complex), which binds exclusively to the X chromosome in Drosophila males and up-regulates the transcription approximately two times.

 

In this thesis I show that roX1 and roX2 are most likely the only non-coding RNAs within the MSL complex. As expected, the roX transcripts were enriched within the MSL complex. Interestingly, one additional transcript was identified within the MSL complex. This transcript did not associate with the X chromosome and is therefore not believed to be involved in up-regulation of the X-linked genes. This transcript encodes for the rate limiting component in the MSL complex, the MSL2 protein. A model is proposed in which free, partial or complete, MSL complex feed-back regulates the amount of msl2 transcript, and thereby limits the MSL complex production.

 

The second chromosome-wide regulatory system in flies acts on an autosome, the heterochromatic 4th chromosome. This regulation is a balancing mechanism between at least two different proteins, the chromosome 4 specific protein painting of fourth (POF) and heterochromatin protein 1 (HP1). POF binds to nascent RNAs transcribed from the 4th chromosome and HP1 target the same set of genes at the chromatin level. POF stimulates the transcribed genes, while HP1 represses them; together they create the most optimal condition for these genes. This type of balancing mechanism may be a more general way to fine-tune transcription at a chromosome-wide level and raises the question about autosomal gene regulation as a general mechanism.

Place, publisher, year, edition, pages
Umeå: Arkitektkopia, 2010. 75 p.
Keyword
Chromatin structure, Drosophila, POF, disage compensation, gene expression, MSL, heterochromatin
National Category
Genetics
Research subject
Genetics
Identifiers
urn:nbn:se:umu:diva-33928 (URN)978-91-7459-017-3 (ISBN)
Public defence
2010-06-04, Major Groove, byggnad 6L, Umeå Universitet, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2010-05-12 Created: 2010-05-10 Last updated: 2011-05-17Bibliographically approved

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Johansson, Anna-MiaStenberg, PerBernhardsson, CarolinaLarsson, Jan

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