Transposable element activation promotes neurodegeneration in a Drosophila model of Huntington's disease

Huntington's disease (HD) is an autosomal dominant disorder with progressive motor dysfunction and cognitive decline. The disease is caused by a CAG repeat expansion in the IT15 gene, which elongates a polyglutamine stretch of the HD protein, Huntingtin. No therapeutic treatments are available, and new pharmacological targets are needed. Retrotransposons are transposable elements (TEs) that represent 40% and 30% of the human and Drosophila genomes and replicate through an RNA intermediate. Mounting evidence suggests that mammalian TEs are active during neurogenesis and may be involved in diseases of the nervous system. Here we show that TE expression and mobilization are increased in a Drosophila melanogaster HD model. By inhibiting TE mobilization with Reverse Transcriptase inhibitors, polyQ-dependent eye neurodegeneration and genome instability in larval brains are rescued and fly lifespan is increased. These results suggest that TE activation may be involved in polyQ-induced neurotoxicity and a potential pharmacological target

Unravelling HP1 functions: post-transcriptional regulation of stem cell fate

Heterochromatin protein 1 (HP1) is a non-histone chromosomal protein first identified in Drosophila as a major component of constitutive heterochromatin, required for stable epigenetic gene silencing in many species including humans. Over the years, several studies have highlighted additional roles of HP1 in different cellular processes including telomere maintenance, DNA replication and repair, chromosome segregation and, surprisingly, positive regulation of gene expression. In this review, we briefly summarize past research and recent results supporting the unexpected and emerging role of HP1 in activating gene expression. In particular, we discuss the role of HP1 in post-transcriptional regulation of mRNA processing because it has proved decisive in the control of germline stem cells homeostasis in Drosophila and has certainly added a new dimension to our understanding on HP1 targeting and functions in epigenetic regulation of stem cell behaviour

A role of the Trx-G complex in Cid/CENP-A deposition at Drosophila melanogaster centromeres

Centromeres are epigenetically determined chromatin structures that specify the assembly site of the kinetochore, the multiprotein machinery that binds microtubules and mediates chromosome segregation during mitosis and meiosis. The centromeric protein A (CENP-A) and its Drosophila orthologue centromere identifier (Cid) are H3 histone variants that replace the canonical H3 histone in centromeric nucleosomes of eukaryotes. CENP-A/Cid is required for recruitment of other centromere and kinetochore proteins and its deficiency disrupts chromosome segregation. Despite the many components that are known to cooperate in centromere function, the complete network of factors involved in CENP-A recruitment remains to be defined. In Drosophila, the Trx-G proteins localize along the heterochromatin with specific patterns and some of them localize to the centromeres of all chromosomes. Here, we show that the Trx, Ash1, and CBP proteins are required for the correct chromosome segregation and that Ash1 and CBP mediate for Cid/CENP-A recruitment at centromeres through post-translational histone modifications. We found that centromeric H3 histone is consistently acetylated in K27 by CBP and that nej and ash1 silencing respectively causes a decrease in H3K27 acetylation and H3K4 methylation along with an impairment of Cid loading

Environmental stress, transposons and evolution

It has been shown that in flies and plants mutations in the stress protein Hsp90 induce a wide spectrum of heritable phenotypic variants. The interpretation was that Hsp90 is a capacitor of morphological evolution and buffers pre-existing genetic variation that is not expressed and accumulates in neutral conditions. This stress-sensitive storage and release of genetic variation by Hsp90 would favour adaptive evolution. However, our recent study has suggested a different explanation of these results (Specchia et al., 2010). It has been demonstrated that Hsp90 is involved in repression of transcription and mobilization of transposable elements in germ cells by affecting piRNA biogenesis. The reduction of HSP90 causes stress response-like activation and transposition of mobile elements along with a wide range of phenotypic variants due to the transposons insertions to the corresponding genes. In addition a molecular analysis of a phenotypic variant, isolated in Hsp90 mutant strain, has also shown a transposon insertion in the corresponding gene. Intriguingly, it has also found that other mutations that impair piRNA biogenesis as capable to induce phenotypic variation. This further indicates that the expression of morphological variability could be related to the disruption of the piRNA silencing mechanism. So that, we proposed that, in general, the stress causes the activation of transposons that induce de novo gene mutations affecting development pathways. Data on the relationship among Stress, mobile elements, genome and epigenomic modifications and their evolutionary significance will be presented

Interaction des sables et Posidonia oceanica avec l'environnement des dunes naturelles - Les syst\ue8mes de d\ue9fense naturels: le potentiel des dunes et des prairies de Posidonie pour la d\ue9fense des littoraux

Dans l'objectif de faire progresser davantage encore les connaissances techniques pour la gestion du syst\ue8me dunes-plages, on propose de mettre en oeuvre des op\ue9rations vis\ue9es au bilan d'exp\ue9rience en mati\ue8re de restauration et de protection des cordons dunaires et \ue0 l'\ue9change d'experiences \ue0 d\ue9velopper dans ce domaine. La protection des dunes coti\ue8res est habituellement approch\ue9e en employant les techniques traditionneles de la protection biotechnique, aptes \ue0 r\ue9duire l'\ue9rosion du vent et l'impact de la pression antropog\ue8ne. Le but de la pr\ue9sente mesure est aussi celui d'\ue9valuer l'efficacit\ue9 de nouvelles technologies biologiques. En suivant cette approche, il est pr\ue9vu le d\ue9clencement des m\ue9canismes positifs de r\ue9troaction entre la biologie et la s\ue9dimentologie, aussi bien qu'une augmentationde la flexibilit\ue9, de la r\ue9silience et de la stabilit\ue9 dynamique du syst\ue8me dunes-plage