DROSOPHILA TELOMERES · Drosophila Telomere Heterochromatin: Gene silencing and Telomere targeting
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2006-09-01 → 2008-08-31
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- IRG
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - DROSOPHILA TELOMERES (Drosophila Telomere Heterochromatin: Gene silencing and Telomere targeting)
The Marie Curie International Reintegration Grant (IRG) has been crucial not only to develop an interesting project that has already resulted in one high rank publication and a second one in preparation but also very important to consolidate the research position of the fellow. Having this grant has allowed me to start my own projects, which will consolidate in two PhD projects from my laboratory (one already started). The Marie Curie IRG funding has been fundamental to pay personnel at the first stages of the grant. Scientifically, the research project has proved that the determinants of the telomere targeting of the Gag protein from the HeT-A telomere retrotransposon, have been conserved in spite a low level of sequence identity. These studies have also shown how the Gag proteins from Drosophila species 60 million years apart are able to recognise the telomeres of each of the studied cell types. All these results resulted in a high rank publication (Casacuberta et al. (2007) Proc. Nat. Acad. Sci. USA, 104, 8391-96). We are also preparing a publication of which telomere components are important for controlling gene expression at the telomere array (composed of the telomere retrotransposons, HeT-A, TART and TAHRE) and not at the subtelomere domain. Moreover, we have obtained results that seem to indicate that not all Drosophila telomeres respond equally to same telomere regulators. We are currently working in establishing which are the molecular mechanisms responsible for the changes in gene expression that we have observed for the different telomere domains. Finally, we are verifying the different protein complexes that have been isolated by creating stable transfected Drosophila Cell lines with the retrotransposon proteins used as baits. After verifying the authenticity of these complexes and their interactions with the telomere retrotransposon proteins, we will be able to better understand the relationship between the telomerase mechanism and the retrotransposon mechanism of telomere maintenance. We will also be able to propose a possible scenario of how the transition from telomerase to the retrotransposon telomere could have taken place in evolution.
Data: CORDIS, © European Union
Project objective
Eukaryote chromosomes are organized in euchromatic and heterochromatic domains that differ in composition and packing level of the chromatin. The genes embedded in heterochromatin are often silenced due to the high level of packing and seem to be activated specifically by different regulators in different heterochromatic domains. Therefore, different requirements and regulatory pathways are likely to exist in different heterochromatic regions. Telomeres are heterochromatic regions composed by DNA and proteins that protect the end of the chromosome of terminal erosion. It is known that telomeres are important in such important processes like tumorogenesis or senescence.With this project I pretend to achieve a better understanding of which mechanisms and path ways control the expression of genes embedded in the telomeres using the Drosophila telomeres as a model. Drosophila telomeres are cytological and functionally equivalent to most eukaryote telomeres, and therefore the obtained results will be of general interest. Nevertheless, Drosophila telomeres are an unusual variation, because instead of using telomerase they are maintained by successive transpositions of two retrotransposons, HeT-A and TART. HeT-A and TART, transpose exclusively to the end of the chromosome, and therefore they have change their parasitic nature into an indispensable cellular role. Till today, it is unknown which are the mechanisms that target HeT-A and TART exclusively to the telomeres.Preliminary results indicate that the Gag protein from HeT-A might be responsible for driving the two telomeric retrotransposons to the end of the chromosome in different Drosophila species. The second part of the proposed project will be dedicated to study in detail the necessity and sufficiency of the H eT-A Gag protein in telomere targeting in Drosophila. Understanding the telomere targeting will be important for the telomere biology but also for possible applications of retrotransposons in gene therapy.
Original text from CORDIS.
Participants
- CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS · MADRIDCoordinatorSpain
Links
Data: CORDIS, © European Union