51 research outputs found
High-Throughput Analysis of Promoter Occupancy Reveals New Targets for Arx, a Gene Mutated in Mental Retardation and Interneuronopathies
Genetic investigations of X-linked intellectual disabilities have implicated the ARX (Aristaless-related homeobox) gene in a wide spectrum of disorders extending from phenotypes characterised by severe neuronal migration defects such as lissencephaly, to mild or moderate forms of mental retardation without apparent brain abnormalities but with associated features of dystonia and epilepsy. Analysis of Arx spatio-temporal localisation profile in mouse revealed expression in telencephalic structures, mainly restricted to populations of GABAergic neurons at all stages of development. Furthermore, studies of the effects of ARX loss of function in humans and animal models revealed varying defects, suggesting multiple roles of this gene during brain development. However, to date, little is known about how ARX functions as a transcription factor and the nature of its targets. To better understand its role, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified a total of 1006 gene promoters bound by Arx in transfected neuroblastoma (N2a) cells and in mouse embryonic brain. Approximately 24% of Arx-bound genes were found to show expression changes following Arx overexpression or knock-down. Several of the Arx target genes we identified are known to be important for a variety of functions in brain development and some of them suggest new functions for Arx. Overall, these results identified multiple new candidate targets for Arx and should help to better understand the pathophysiological mechanisms of intellectual disability and epilepsy associated with ARX mutations
Immune Response and Mitochondrial Metabolism Are Commonly Deregulated in DMD and Aging Skeletal Muscle
Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors
Meta-analysis of muscle transcriptome data using the MADMuscle database reveals biologically relevant gene patterns
<p>Abstract</p> <p>Background</p> <p>DNA microarray technology has had a great impact on muscle research and microarray gene expression data has been widely used to identify gene signatures characteristic of the studied conditions. With the rapid accumulation of muscle microarray data, it is of great interest to understand how to compare and combine data across multiple studies. Meta-analysis of transcriptome data is a valuable method to achieve it. It enables to highlight conserved gene signatures between multiple independent studies. However, using it is made difficult by the diversity of the available data: different microarray platforms, different gene nomenclature, different species studied, etc.</p> <p>Description</p> <p>We have developed a system tool dedicated to muscle transcriptome data. This system comprises a collection of microarray data as well as a query tool. This latter allows the user to extract similar clusters of co-expressed genes from the database, using an input gene list. Common and relevant gene signatures can thus be searched more easily. The dedicated database consists in a large compendium of public data (more than 500 data sets) related to muscle (skeletal and heart). These studies included seven different animal species from invertebrates (<it>Drosophila melanogaster, Caenorhabditis elegans</it>) and vertebrates (<it>Homo sapiens, Mus musculus, Rattus norvegicus, Canis familiaris, Gallus gallus</it>). After a renormalization step, clusters of co-expressed genes were identified in each dataset. The lists of co-expressed genes were annotated using a unified re-annotation procedure. These gene lists were compared to find significant overlaps between studies.</p> <p>Conclusions</p> <p>Applied to this large compendium of data sets, meta-analyses demonstrated that conserved patterns between species could be identified. Focusing on a specific pathology (Duchenne Muscular Dystrophy) we validated results across independent studies and revealed robust biomarkers and new pathways of interest. The meta-analyses performed with MADMuscle show the usefulness of this approach. Our method can be applied to all public transcriptome data.</p
Un district antimono-aurifÚre à gangue quartzo-carbonatée le Semnon (Ille et Vilaine, massif armoricain, France)
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Atlas de l'archipel de MoleÌne : geÌologie, geÌomorphologie et seÌdimentologie
National audienceProlongement occidental du domaine lĂ©onard, lâarchipel de MolĂšne est une constellation dâĂźles et dâĂźlots, peu connus du grand public, et regroupĂ©s en un vaste plateau sous-marin. GrĂące Ă des investigations nombreuses et diversifiĂ©es, des scientifiques brestois de lâIfremer, de lâUBO et du CNRS ont obtenu des rĂ©sultats tout Ă fait originaux sur les environnements gĂ©ologique, gĂ©omorphologique et sĂ©dimentologique de lâarchipel.Lâatlas se compose dâun livret et de 3 cartes thĂ©matiques (au format papier et leurs Ă©quivalents numĂ©riques sur clĂ© USB), illustrant trois grands volets de la trĂšs longue histoire de lâarchipel. Celle-ci sâĂ©chelonne sur environ 300 millions dâannĂ©es, du PalĂ©ozoĂŻque jusquâĂ nos jours. Les principaux Ă©vĂšnements magmatiques, tectoniques et mĂ©tamorphiques, liĂ©s Ă la formation de la chaĂźne de montagnes hercynienne Ă la fin de lâĂšre palĂ©ozoĂŻque, sont dĂ©crits. LâĂ©volution de lâarchipel au cours des derniers milliers dâannĂ©es est Ă©galement retracĂ©e. La dynamique rĂ©cente du cordon littoral et celle du domaine sous-marin profond sont dĂ©voilĂ©es, tout comme la nature et la distribution des sĂ©diments qui les composent.Ces documents, tous inĂ©dits, sâadressent Ă une large communautĂ© dâutilisateurs, allant des professionnels de la pĂȘche et de la plaisance, aux amĂ©nageurs, bureaux dâĂ©tudes, dĂ©cideurs publics, gestionnaires dâespaces protĂ©gĂ©s, mais aussi Ă quiconque est sensibilisĂ© Ă la protection de lâenvironnement littoral et marin. Par la densitĂ© et lâoriginalitĂ© des rĂ©sultats prĂ©sentĂ©s, sâappuyant sur une riche iconographie, cet atlas sera une rĂ©fĂ©rence pour de futurs travaux
Atlas de l'archipel de MoleÌne : geÌologie, geÌomorphologie et seÌdimentologie
National audienceProlongement occidental du domaine lĂ©onard, lâarchipel de MolĂšne est une constellation dâĂźles et dâĂźlots, peu connus du grand public, et regroupĂ©s en un vaste plateau sous-marin. GrĂące Ă des investigations nombreuses et diversifiĂ©es, des scientifiques brestois de lâIfremer, de lâUBO et du CNRS ont obtenu des rĂ©sultats tout Ă fait originaux sur les environnements gĂ©ologique, gĂ©omorphologique et sĂ©dimentologique de lâarchipel.Lâatlas se compose dâun livret et de 3 cartes thĂ©matiques (au format papier et leurs Ă©quivalents numĂ©riques sur clĂ© USB), illustrant trois grands volets de la trĂšs longue histoire de lâarchipel. Celle-ci sâĂ©chelonne sur environ 300 millions dâannĂ©es, du PalĂ©ozoĂŻque jusquâĂ nos jours. Les principaux Ă©vĂšnements magmatiques, tectoniques et mĂ©tamorphiques, liĂ©s Ă la formation de la chaĂźne de montagnes hercynienne Ă la fin de lâĂšre palĂ©ozoĂŻque, sont dĂ©crits. LâĂ©volution de lâarchipel au cours des derniers milliers dâannĂ©es est Ă©galement retracĂ©e. La dynamique rĂ©cente du cordon littoral et celle du domaine sous-marin profond sont dĂ©voilĂ©es, tout comme la nature et la distribution des sĂ©diments qui les composent.Ces documents, tous inĂ©dits, sâadressent Ă une large communautĂ© dâutilisateurs, allant des professionnels de la pĂȘche et de la plaisance, aux amĂ©nageurs, bureaux dâĂ©tudes, dĂ©cideurs publics, gestionnaires dâespaces protĂ©gĂ©s, mais aussi Ă quiconque est sensibilisĂ© Ă la protection de lâenvironnement littoral et marin. Par la densitĂ© et lâoriginalitĂ© des rĂ©sultats prĂ©sentĂ©s, sâappuyant sur une riche iconographie, cet atlas sera une rĂ©fĂ©rence pour de futurs travaux
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