Éditeur(s) : Université des Antilles AREBio Groupe de recherche BIOSPHERES : BIOlogie, Sciences Physiques & Humaines pour les énergies Renouvelables, l
Extrait de : 1er colloque international BIOSPHERES, du 18 au 20 juin 2019. Université des Antilles
Description : Drosophila often offers many advantages as an experimental organism. The dead ringer (dri) gene of drosophila melanogaster is a member of the recently discovered ARID-box family of eukaryotic genes that encodes proteins with a conserved DNA-binding domain. dri itself is highly well conserved with specific orthologs from human to yeast genomes. This family include ARID3A, 3B and 3C with have role in embryonic pattening, cell lineage gene regulation, cell cycle control, transcriptional regulation and chromatin structure modification. We first showed that the gene encoding ARID3A also known as Bright (B cell regulator of immunoglobulin heavy chain transcription) play critical roles in B-cell development and SATB1 in T-cell transcription regulation. In this international workshops we will expose a comprehensive understanding of these molecules and better knowledge of their specific targets and function-interactions in controlling cell fate decisions and development. In addition, dri have homology with the Aedes aegypti mosquitoes which had ability to carry and spread disease to human. More than half of the world?s population live in areas where this mosquito species is present, including Martinique. Sustained mosquito control efforts are important to prevent outbreaks from Dengue, Chikungunya, malaria, zika diseases. Discovering the functions of AT-rich genes in preventing illness from mosquito is the central goal for raising working progress hypothesis.

Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V19077
V19077

Éditeur(s) : Springer
Résumé : The transforming growth factor (TGF)-beta superfamily is a group of important growth factors involved in multiple processes such as differentiation, cell proliferation, apoptosis and cellular growth. In the Pacific oyster Crassostrea gigas, the oyster gonadal (og) TGF-beta gene was recently characterized through genome-wide expression profiling of oyster lines selected to be resistant or susceptible to summer mortality. Og TGF-beta appeared specifically expressed in the gonad to reach a maximum when gonads are fully mature, which singularly contrasts with the pleiotropic roles commonly ascribed to most TGF-beta family members. The function of og TGF-beta protein in oysters is unknown, and defining its role remains challenging. In this study, we develop a rapid bacterial production system to obtain recombinant og TGF-beta protein, and we demonstrate that og TGF-beta is processed by furin to a mature form of the protein. This mature form can be detected in vivo in the gonad. Functional inhibition of mature og TGF-beta in the gonad was conducted by inactivation of the protein using injection of antibodies. We show that inhibition of og TGF-beta function tends to reduce gonadic area. We conclude that mature og TGF-beta probably functions as an activator of germ cells development in oyster.
Marine Biotechnology (1436-2228) (Springer), 2011-10 , Vol. 13 , N. 5 , P. 971-980

Droits : Springer Science+Business Media, LLC 2011
http://archimer.ifremer.fr/doc/00042/15371/13438.pdf
DOI:10.1007/s10126-010-9361-4
http://archimer.ifremer.fr/doc/00042/15371/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: Until recently, synonymous mutations (which do not change amino acids) have been much neglected. Some evidence suggests that this kind of mutations could affect mRNA secondary structure or stability, translation kinetics and protein structure. To explore deeper the role of synonymous mutations, we studied their consequence on the functional activity of the estrogen receptor alpha (ERα). The ERα is a ligand-inducible transcription factor that orchestrates pleiotropic cellular effects, at both genomic and non-genomic levels in response to estrogens. In this work we analyzed in transient transfection experiments, the activity of ERα carrying the synonymous mutation Ala87, a polymorphism involving about 5-10% of the population. In comparison to the wild type receptor, our results show that ERαA87 mutation reduces the transactivation efficiency of ERα on an ERE reporter gene while its expression level remains similar. This mutation enhances 4-OHT-induced transactivation of ERα on an AP1 reporter gene. Finally, the mutation affects the subcellular localization of ERα in a cell type specific manner. It enhances the cytoplasmic location of ERα without significant changes in non-genomic effects of E2. The functional alteration of the ERαA87 determined in this work highlights the relevance of synonymous mutations for biomedical and pharmacological points of view.
Journal of steroid biochemistry and molecular biology

inserm-01015532
http://www.hal.inserm.fr/inserm-01015532
DOI : 10.1016/j.jsbmb.2014.02.016
PUBMED : 24607813

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
The retroviral genome consists of an intron-containing transcript that has essential cytoplasmic functions in the infected cell. This viral transcript can escape splicing, circumvent the nuclear checkpoint mechanisms and be transported to the cytoplasm by hijacking the host machinery. Once in the cytoplasm, viral unspliced RNA acts as mRNA to be translated and as genomic RNA to be packaged into nascent viruses. The murine leukemia virus (MLV) is among the first retroviruses discovered and is classified as simple Retroviridae due to its minimal encoding capacity. The oncogenic and transduction abilities of MLV are extensively studied, whereas surprisingly the crucial step of its nuclear export has remained unsolved until 2014. Recent work has revealed the recruitment by MLV of the cellular NXF1/Tap-dependent pathway for export. Unconventionally, MLV uses of Tap to export both spliced and unspliced viral RNAs. Unlike other retroviruses, MLV does not harbor a unique RNA signal for export. Indeed, multiple sequences throughout the MLV genome appear to promote export of the unspliced MLV RNA. We review here the current understanding of the export mechanism and highlight the determinants that influence MLV export. As the molecular mechanism of MLV export is elucidated, we will gain insight into the contribution of the export pathway to the cytoplasmic fate of the viral RNA
ISSN: 1547-6286

hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/file/Insights%20into%20the%20nuclear%20export%20of%20murine%20leukemia%20virus%20intron-containing%20RNA.pdf
DOI : 10.1080/15476286.2015.1065375

Éditeur(s) : HAL CCSD
Résumé : International audience
Symbiosis is a widespread phenomenon in the biosphere. In marine benthic environments breakdown of symbiosis is responsible for coral bleaching and dramatically affects coral reef ecosystems functioning [1]. In the water column, planktonic organisms are key component of pelagic ecosystems and a number of species form mutualistic association with microalgae forming a photosymbiosis [2]. Here we intended to investigate the genetic basis of photosymbiosis, through a transcriptomic approach on marine plankton organisms. We focused more specifically on associations occurring between radiolarian host (protist, zooplankton) and dinoflagellates symbiont (protist, phytoplankton) living inside the host cell. It has recently been highlighted that these holobionts are widespread in oligotrophic open oceans and there are also evidences of their fundamental implication in biogeochemical carbon, silica and strontium cycles [3, 4, 5, 6]. RNA-seq technologies allow obtaining an unprecedented amount of data for unicellular organisms isolated from the environment [7]. The study of such non-model holobionts datasets requires de novo assembly, which implies considerable computational resources and the potential production of chimeric sequences [8, 9].We therefore developed an original strategy aiming at accelerating and improving de novo assembly for holobiont datasets. We chose SIMKA [10] a fast kmer-based method initially developed to estimate the similarity between numerous metagenomic datasets, and which has been recently adapted to extract their common sequences. As our symbionts are identified, we used SIMKA to compare our holobionts transcriptomes to publicly available dinoflagellates transcriptomes [11] generating two datasets, one composed of reads from the symbionts and another with reads from the host (for which no reference data are currently available). Independent assemblies were then performed in parallel, accelerating the study process, and minimizing the proportion of resulting chimeric sequences. Our strategy produced a unique and comprehensive genomic dataset for Radiolaria [12, 13], and offers a pragmatic, large scale, comparison strategy to assemble and study holobionts [9]. Our new sequences obtained from holobionts study will be used for phylogenomics investigation, as reference for environmental metagenomic studies and ultimately to understand and characterize the molecular basis of symbiotic relationships in the plankton.Bibliografic references :[1] Simon K. Davy, Denis Allemand, and Virginia M. Weis. “Cell Biology of Cnidarian-Dinoflagellate Symbiosis”. In: Microbiology and Molecular Biology Reviews 76.2 (June 1, 2012), pp. 229–261. issn: 1092-2172, 1098- 5557. doi: 10.1128/MMBR.05014-11.[2] Janouškovec, J. et al. “Major transitions in dinoflagellate evolution unveiled by phylotranscriptomics”. in: PNAS 201614842 (2016). doi:10.1073/pnas.1614842114[3] Tristan Biard et al. “In situ imaging reveals the biomass of giant protists in the global ocean”. In: Nature advance online publication (Apr. 20, 2016). issn: 0028-0836. doi: 10.1038/nature17652.[4] Lionel Guidi et al. “Plankton networks driving carbon export in the olig- otrophic ocean”. In: Nature 532.7600 (Apr. 28, 2016), pp. 465–470. issn: 0028-0836. doi: 10.1038/nature16942.[5] Diane K. Stoecker et al. “Acquired phototrophy in aquatic protists”. In: Aquatic Microbial Ecology 57.3 (Nov. 24, 2009), pp. 279–310. doi: 10.3354/ame01340.[6] Johan Decelle et al. “An original mode of symbiosis in open ocean plankton”. In: Proceedings of the National Academy of Sciences 109.44 (Oct. 30, 2012), pp. 18000–18005. issn: 0027-8424, 1091-6490. doi: 10. 1073/pnas.1212303109.[7] Sergio Balzano et al. “Transcriptome analyses to investigate symbiotic relationships between marine protists”. In: Frontiers in Microbiology 6 (Mar. 17, 2015). issn: 1664-302X. doi: 10.3389/fmicb.2015.00098.[8] Li, B. et al. “Evaluation of de novo transcriptome assemblies from RNA-Seq data”. In: Genome Biology 15, 553 (2014).[9] Sangwan, N., Xia, F. & Gilbert, J. A. “Recovering complete and draft population genomes from metagenome datasets”. In: Microbiome 4, 8 (2016).[10] Gaëtan Benoit et al. “Multiple comparative metagenomics using mul- tiset k -mer counting”. In: PeerJ Computer Science 2 (Nov. 14, 2016). doi: 10.7717/peerj-cs.94.[11] Patrick J. Keeling et al. “The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): Illuminating the Functional Diversity of Eukaryotic Life in the Oceans through Transcriptome Sequencing”. In: PLOS Biol 12.6 (June 2014), e1001889. issn: 1545-7885. doi: 10.1371/journal.pbio.1001889.[12] Burki, F. et al. “Evolution of Rhizaria: new insights from phylogenomic analysis of uncultured protists”. In BMC Evolutionary Biology 10, 377 (2010).
International Conference on Holobionts
Paris, France

hal-01575069
https://hal.inria.fr/hal-01575069

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: The insecticide chlordecone was extensively used in the French West Indies to control banana root borer. Its persistence in soils has led to the widespread pollution of the environment, and human beings are still exposed to this chemical. Chlordecone has been shown to impair neurological and behavioural functions in rodents when exposed gestationally or neonatally. OBJECTIVES: The aim of the study was to evaluate the impact of prenatal and postnatal exposure to chlordecone on the cognitive, visual, and motor development of 7-month-old infants from Guadeloupe. METHODS: Infants were tested at 7 months (n=153). Visual recognition memory and processing speed were assessed with the Fagan Tests of Infant Intelligence (FTII), visual acuity with the Teller Acuity Card, and fine motor development with the Brunet-Lezine. Samples of cord blood and breast milk at 3 months (n=88) were analyzed for chlordecone concentrations. Postnatal exposure was determined through breast feeding and frequency of contaminated food consumption by the infants. RESULTS: Cord chlordecone concentrations in tertiles were associated with reduced novelty preference on the FTII in the highly exposed group (β=-0.19, p=0.02). Postnatal exposure through contaminated food consumption was marginally related to reduced novelty preference (β=-0.14, p=0.07), and longer processing speed (β=0.16, p=0.07). Detectable levels of chlordecone in cord blood were associated with higher risk of obtaining low scores on the fine motor development scale (OR=1.25, p<0.01). CONCLUSION: These results suggest that pre- and postnatal low chronic exposure to chlordecone is associated with negative effects on cognitive and motor development during infancy.
ISSN: 0013-9351

hal-00875939
https://hal.archives-ouvertes.fr/hal-00875939
DOI : 10.1016/j.envres.2012.07.006
PUBMED : 22910562

Éditeur(s) : HAL CCSD Wiley
Résumé : The evolutionary potential of long-lived species, such as forest trees, is fundamental for their local persistence under climate change (CC). Genome–environment association (GEA) analyses reveal if species in heterogeneous environments at the regional scale are under differential selection resulting in populations with potential preadaptation to CC within this area. In 79 natural [i]Fagus sylvatica[/i] populations, neutral genetic patterns were characterized using 12 simple sequence repeat (SSR) markers, and genomic variation (144 single nucleotide polymorphisms (SNPs) out of 52 candidate genes) was related to 87 environmental predictors in the latent factor mixed model, logistic regressions and isolation by distance/environmental (IBD/IBE) tests. SSR diversity revealed relatedness at up to 150m intertree distance but an absence of large-scale spatial genetic structure and IBE. In the GEA analyses, 16 SNPs in 10 genes responded to one or several environmental predictors and IBE, corrected for IBD, was confirmed. The GEA often reflected the proposed gene functions, including indications for adaptation to water availability and temperature. Genomic divergence and the lack of large-scale neutral genetic patterns suggest that gene flow allows the spread of advantageous alleles in adaptive genes. Thereby, adaptation processes are likely to take place in species occurring in heterogeneous environments, which might reduce their regional extinction risk under CC
ISSN: 0028-646X

hal-01309135
https://hal.archives-ouvertes.fr/hal-01309135
PRODINRA : 343710
DOI : 10.1111/nph.13809

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival. METHODS: Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes. The results of expression quantitative trait locus (eQTL) analyses were also replicated with a Gene Expression Omnibus (GEO) data set. The effects of eQTLs on overall survival (OS) and disease-free survival (DFS) were evaluated. RESULTS: Five ancestry-related SNPs were identified as cis-eQTLs in the DNA polymerase beta (POLB) gene (false discovery rate [FDR]<0.01). The homozygous/heterozygous genotypes containing the African allele showed higher POLB expression than the homozygous white allele genotype (P<.001). A replication study using a GEO data set validated all 5 eQTLs and also showed a statistically significant difference in POLB expression based on genetic ancestry (P=.002). An association was observed between these eQTLs and OS (P<.037; FDR<0.0363) as well as DFS (P=.018 to.0629; FDR<0.079) for oral cavity and laryngeal cancer patients treated with platinum-based chemotherapy and/or radiotherapy. Genotypes containing the African allele were associated with poor OS/DFS in comparison with homozygous genotypes harboring the white allele. CONCLUSIONS: Analyses show that ancestry-related alleles could act as eQTLs in HNSCC and support the association of ancestry-related genetic factors with survival disparities in patients diagnosed with oral cavity and laryngeal cancer. (C) 2016 American Cancer Society.
ISSN: 0008-543X

hal-01519253
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519253
DOI : 10.1002/cncr.30457
PUBMED : 27906459

Éditeur(s) : HAL CCSD Society for Molecular Biology and Evolution
Résumé : International audience
Complex nongradual evolutionary processes such as gene remodeling are difficult to model, to visualize, and to investigate systematically. Despite these challenges, the creation of composite (or mosaic) genes by combination of genetic segments from unrelated gene families was established as an important adaptive phenomena in eukaryotic genomes. In contrast, almost no general studies have been conducted to quantify composite genes in viruses. Although viral genome mosaicism has been well-described, the extent of gene mosaicism and its rules of emergence remain largely unexplored. Applying methods from graph theory to inclusive similarity networks, and using data from more than 3,000 complete viral genomes, we provide the first demonstration that composite genes in viruses are 1) functionally biased, 2) involved in key aspects of the arm race between cells and viruses, and 3) can be classified into two distinct types of composite genes in all viral classes. Beyond the quantification of the widespread recombination of genes among different viruses of the same class, we also report a striking sharing of genetic information between viruses of different classes and with different nucleic acid types. This latter discovery provides novel evidence for the existence of a large and complex mobilome network, which appears partly bound by the sharing of genetic information and by the formation of composite genes between mobile entities with different genetic material. Considering that there are around 10E31 viruses on the planet, gene remodeling appears as a hugely significant way of generating and moving novel sequences between different kinds of organisms on Earth.
ISSN: 1759-6653

Droits : http://creativecommons.org/licenses/by/
hal-01324848
http://hal.upmc.fr/hal-01324848
http://hal.upmc.fr/hal-01324848/document
http://hal.upmc.fr/hal-01324848/file/Genome%20Biol%20Evol-2014-Jachiet-2195-205.pdf
DOI : 10.1093/gbe/evu168

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Genetics and molecular biology have been instrumental for a better understanding of heritable defects causing human infertility over the past decades. More recently, the field of reproductive biology has harnessed genome biological approaches to gain insight into molecular processes underlying normal and pathological gametogenesis and gamete function. We are currently witnessing yet another quantum leap in our ability to monitor the flow of information from the genome via the transcriptome to the proteome: tiling arrays that cover both strands of a given target genome and RNA-Seq, a method based on ultra-high throughput DNA sequencing, enable us to study noncoding and protein-coding transcripts with unprecedented precision and depth at a reasonable cost. These technologies have spawned a thriving discipline within the bioinformatics field that employs information technology for managing and interpreting biological high-throughput data. This review outlines database projects and online analysis tools useful for life scientists in general and discusses in detail selected projects that have specifically been developed for researchers and clinicians in the field of reproductive biology. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.
ISSN: 0006-3002

hal-00877444
https://hal.archives-ouvertes.fr/hal-00877444
DOI : 10.1016/j.bbadis.2012.05.018
PUBMED : 22687534

Éditeur(s) : HAL CCSD BioMed Central
Résumé : [b]Background[/b][br/] [br/] The Amazonian rainforest is predicted to suffer from ongoing environmental changes. Despite the need to evaluate the impact of such changes on tree genetic diversity, we almost entirely lack genomic resources.[br/] [br/] [b]Results[/b][br/] [br/] In this study, we analysed the transcriptome of four tropical tree species (Carapa guianensis, Eperua falcata, Symphonia globulifera and Virola michelii) with contrasting ecological features, belonging to four widespread botanical families (respectively Meliaceae, Fabaceae, Clusiaceae and Myristicaceae). We sequenced cDNA libraries from three organs (leaves, stems, and roots) using 454 pyrosequencing. We have developed an R and bioperl-based bioinformatic procedure for de novo assembly, gene functional annotation and marker discovery. Mismatch identification takes into account single-base quality values as well as the likelihood of false variants as a function of contig depth and number of sequenced chromosomes. Between 17103 (for Symphonia globulifera) and 23390 (for Eperua falcata) contigs were assembled. Organs varied in the numbers of unigenes they apparently express, with higher number in roots. Patterns of gene expression were similar across species, with metabolism of aromatic compounds standing out as an overrepresented gene function. Transcripts corresponding to several gene functions were found to be over- or underrepresented in each organ. We identified between 4434 (for Symphonia globulifera) and 9076 (for Virola surinamensis) well-supported mismatches. The resulting overall mismatch density was comprised between 0.89 (S. globulifera) and 1.05 (V. surinamensis) mismatches/100 bp in variation-containing contigs.[br/] [br/] [b]Conclusion[/b][br/] [br/] The relative representation of gene functions in the four transcriptomes suggests that secondary metabolism may be particularly important in tropical trees. The differential representation of transcripts among tissues suggests differential gene expression, which opens the way to functional studies in these non-model, ecologically important species. We found substantial amounts of mismatches in the four species. These newly identified putative variants are a first step towards acquiring much needed genomic resources for tropical tree species.
ISSN: 1471-2164

hal-01032439
https://hal.archives-ouvertes.fr/hal-01032439
https://hal.archives-ouvertes.fr/hal-01032439/document
https://hal.archives-ouvertes.fr/hal-01032439/file/art_10-1186_1471-2164-15-238.pdf
DOI : 10.1186/1471-2164-15-238

Éditeur(s) : HAL CCSD Society for Molecular Biology and Evolution
Résumé : International audience
Microsatellites (SSRs) are highly susceptible to expansions and contractions. When located in a coding sequence, the insertion or the deletion of a single unit for a mono-, di-, tetra-, or penta(nucleotide)-SSR creates a frameshift. As a consequence, one would expect to find only very few of these SSRs in coding sequences because of their strong deleterious potential. Unexpectedly, genomes contain many coding SSRs of all types. Here, we report on a study of their evolution in a phylogenetic context using the genomes of four primates: human, chimpanzee, orangutan, and macaque. In a set of 5,015 orthologous genes unambiguously aligned among the four species, we show that, except for tri- and hexa-SSRs, for which insertions and deletions are frequently observed, SSRs in coding regions evolve mainly by substitutions. We show that the rate of substitution in all types of coding SSRs is typically two times higher than in the rest of coding sequences. Additionally, we observe that although numerous coding SSRs are created and lost by substitutions in the lineages, their numbers remain constant. This last observation suggests that the coding SSRs have reached equilibrium. We hypothesize that this equilibrium involves a combination of mutation, drift, and selection. We thus estimated the fitness cost of mono-SSRs and show that it increases with the number of units. We finally show that the cost of coding mono-SSRs greatly varies from function to function, suggesting that the strength of the selection that acts against them can be correlated to gene functions.
ISSN: 1759-6653

hal-01544762
https://hal.archives-ouvertes.fr/hal-01544762
DOI : 10.1093/gbe/evt003

Éditeur(s) : HAL CCSD
Résumé : International audience
Spermatogenesis is a highly sophisticated process involved in the transmission of genetic heritage. It includes halving ploidy, repackaging of the chromatin for transport, and the equipment of developing spermatids and eventually spermatozoa with the advanced apparatus (e.g., tightly packed mitochondrial sheat in the mid piece, elongating of the tail, reduction of cytoplasmic volume) to elicit motility once they reach the epididymis. Mammalian spermatogenesis is divided into three phases. In the first the primitive germ cells or spermatogonia undergo a series of mitotic divisions. In the second the spermatocytes undergo two consecutive divisions in meiosis to produce haploid spermatids. In the third the spermatids differentiate into spermatozoa in a process called spermiogenesis. Paracrine, autocrine, juxtacrine, and endocrine pathways all contribute to the regulation of the process. The array of structural elements and chemical factors modulating somatic and germ cell activity is such that the network linking the various cellular activities during spermatogenesis is unimaginably complex. Over the past two decades, advances in genomics have greatly improved our knowledge of spermatogenesis, by identifying numerous genes essential for the development of functional male gametes. Large-scale analyses of testicular function have deepened our insight into normal and pathological spermatogenesis. Progress in genome sequencing and microarray technology have been exploited for genome-wide expression studies, leading to the identification of hundreds of genes differentially expressed within the testis. However, although proteomics has now come of age, the proteomics-based investigation of spermatogenesis remains in its infancy. Here, we review the state-of-the-art of large-scale proteomic analyses of spermatogenesis, from germ cell development during sex determination to spermatogenesis in the adult. Indeed, a few laboratories have undertaken differential protein profiling expression studies and/or systematic analyses of testicular proteomes in entire organs or isolated cells from various species. We consider the pros and cons of proteomics for studying the testicular germ cell gene expression program. Finally, we address the use of protein datasets, through integrative genomics (i.e., combining genomics, transcriptomics, and proteomics), bioinformatics, and modelling.
Systems Biology in Reproductive Medicine

hal-00877749
https://hal.archives-ouvertes.fr/hal-00877749
DOI : 10.3109/19396368.2012.691943
PUBMED : 22788530

Éditeur(s) : HAL CCSD
Résumé : The recent accumulation of genomic sequence data has shown that gene evolution is not strictly tree-Like. Many evolutionary processes, like exon shuffling, gene fusion or nonhomologous recombination remodel genes by creating composite structures that are made from parts with different evolutionary histories. The development of sequence similarity networks provides an analytical framework to study the impact of these processes on molecular evolution, by structuring the resemblance relationships between sequences and by formalizing, in terms of graph theory, the detection of composite genes (intransitive triplets) and gene families (clique minimal separators). The size of current data sets, typically several million sequences, has also required the development of new tools and methods: sequence comparison parallelization, large networks visualization with Louvain communities and large cycles identification. When applied to eukaryotic and viral genome data sets, these methods have shown that composite genes are found throughout cellular organisms and mobile genetic elements. Proportionally, composite genes are more numerous in eukaryotic genomes; in absolute number, they are more numerous in viruses. In the latter, composite genes functional distribution is biased (enrichment of genes families that are essential for the perpetuation of the viral cycle), and the various parts of composite genes sometimes even originate from the genetic material of different viral classes. More generally, the extent of combinatorial processes, by unravelling other evolutionary bonds than homology bonds in the strictest sense, legitimates a pluralistic study of similarity relationships between sequences.
L’accumulation récente de données de séquences génomiques a montré que l’évolution des gènes n’est pas strictement arborescente. De nombreux processus évolutifs, comme l’exon shuffling, la fusion de gènes ou la recombinaison illégitime remodèlent les gènes, créant des structures composites, formées de parties dont les histoires évolutives sont différentes. Le développement de réseaux de similarité de séquences fournit un cadre analytique permettant d’étudier l’impact de ces processus sur l’évolution moléculaire, en structurant les relations de ressemblance entre séquences et en formalisant en termes de graphes la détection de gènes (triplets intransitifs) et de familles de gènes (cliques minimales séparatrices) composites. La taille des jeux de données actuels, de l’ordre de plusieurs millions de séquences, a également requis le développement de nouveaux outils et méthodes : parallélisation des comparaisons de séquences, visualisation de très grands réseaux par simplification en communautés de Louvain et identification de grands cycles. Appliquées à des jeux de données de génomes eucaryotes et viraux, ces méthodes ont démontré la présence de gènes composites dans tout le vivant et les éléments génétiques mobiles. En proportion, les gènes composites sont plus nombreux dans les génomes eucaryotes ; en nombre absolu, ils sont plus nombreux à être portés par des virus. Chez ces derniers, la distribution fonctionnelle des gènes composites est biaisée (enrichissement dans les familles essentielles pour la perpétuation du cycle viral), et les éléments des gènes composites trouvent même parfois leurs origines dans le matériel génétique de classes virales différentes. Plus généralement, l’étendue des processus combinatoires, en révélant des liens évolutionnaires autres que les liens d’homologie au sens fort, justifie une étude pluraliste des relations de similarité entre séquences.
https://tel.archives-ouvertes.fr/tel-01127379

NNT : 2014PA066358
tel-01127379
https://tel.archives-ouvertes.fr/tel-01127379
https://tel.archives-ouvertes.fr/tel-01127379/document
https://tel.archives-ouvertes.fr/tel-01127379/file/2014PA066358.pdf

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Genetic recombination occurs during meiosis, the key developmental programme of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyltransferase, PR domain containing 9 (PRDM9), the product of the only known speciation-associated gene in mammals. PRDM9 is thought to determine the preferred recombination sites--recombination hotspots--through sequence-specific binding of its highly polymorphic multi-Zn-finger domain. Nevertheless, Prdm9 knockout mice are proficient at initiating recombination. Here we map and analyse the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F(1) hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the exception of the pseudo-autosomal region (PAR)--the only area of the genome that undergoes recombination in 100% of cells. Surprisingly, hotspots are still observed in Prdm9 knockout mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4) trimethylation marks. However, in the absence of PRDM9, most recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice, indicating an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements.
ISSN: 0028-0836

hal-00877666
https://hal.archives-ouvertes.fr/hal-00877666
DOI : 10.1038/nature11089
PUBMED : 22660327

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background : Trichoderma reesei is the main industrial source of cellulases and hemicellulases required for the hydrolysis of biomass to simple sugars, which can then be used in the production of biofuels and biorefineries. The highly productive strains in use today were generated by classical mutagenesis. As byproducts of this procedure, mutants were generated that turned out to be unable to produce cellulases. In order to identify the mutations responsible for this inability, we sequenced the genome of one of these strains, QM9136, and compared it to that of its progenitor T. reesei QM6a.Results : In QM9136, we detected a surprisingly low number of mutagenic events in the promoter and coding regions of genes, i.e. only eight indels and six single nucleotide variants. One of these indels led to a frame-shift in the Zn2Cys6 transcription factor XYR1, the general regulator of cellulase and xylanase expression, and resulted in its C-terminal truncation by 140 amino acids. Retransformation of strain QM9136 with the wild-type xyr1 allele fully recovered the ability to produce cellulases, and is thus the reason for the cellulase-negative phenotype. Introduction of an engineered xyr1 allele containing the truncating point mutation into the moderate producer T. reesei QM9414 rendered this strain also cellulase-negative. The correspondingly truncated XYR1 protein was still able to enter the nucleus, but failed to be expressed over the basal constitutive level.Conclusion : The missing 140 C-terminal amino acids of XYR1 are therefore responsible for its previously observed auto-regulation which is essential for cellulases to be expressed. Our data present a working example of the use of genome sequencing leading to a functional explanation of the QM9136 cellulase-negative phenotype.
ISSN: 1471-2164

Droits : http://creativecommons.org/licenses/by/
hal-01149671
http://hal.upmc.fr/hal-01149671
http://hal.upmc.fr/hal-01149671/document
http://hal.upmc.fr/hal-01149671/file/Lichius_2015_Genome_sequencing.pdf
DOI : 10.1186/s12864-015-1526-0

Éditeur(s) : HAL CCSD American Association for the Advancement of Science
Résumé : International audience
DNA double-strand breaks (DSBs) are introduced in meiosis to initiate recombination and generate crossovers, the reciprocal exchanges of genetic material between parental chromosomes. Here, we present high-resolution maps of meiotic DSBs in individual human genomes. Comparing DSB maps between individuals shows that along with DNA binding by PRDM9, additional factors may dictate the efficiency of DSB formation. We find evidence for both GC-biased gene conversion and mutagenesis around meiotic DSB hotspots, while frequent colocalization of DSB hotspots with chromosome rearrangement breakpoints implicates the aberrant repair of meiotic DSBs in genomic disorders. Furthermore, our data indicate that DSB frequency is a major determinant of crossover rate. These maps provide new insights into the regulation of meiotic recombination and the impact of meiotic recombination on genome function.
ISSN: 0036-8075

hal-01123717
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01123717
PUBMED : 25395542
DOI : 10.1126/science.1256442

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
Transcriptional regulation by the estrogen receptor-alpha(ER) has been investigated mainly in breast cancer cell lines, but estrogens such as 17 beta-estradiol (E2) exert numerous extrareproductive effects, particularly in the liver, where E2 exhibits both protective metabolic and deleterious thrombotic actions. To analyze the direct and early transcriptional effects of estrogens in the liver, we determined the E2-sensitive transcriptome and ER cistrome in mice after acute administration of E2 or placebo. These analyses revealed the early induction of genes involved in lipid metabolism, which fits with the crucial role of ER in the prevention of liver steatosis. Characterization of the chromatin state of ER binding sites (BSs) in mice expressing or not ER demonstrated that ER is not required per se for the establishment and/or maintenance of chromatin modifications at the majority of its BSs. This is presumably a consequence of a strong overlap between ER and hepatocyte nuclear factor 4 alpha BSs. In contrast, 40% of the BSs of the pioneer factor forkhead box protein a (Foxa2) were dependent upon ER expression, and ER expression also affected the distribution of nucleosomes harboring dimethylated lysine 4 of Histone H3 around Foxa2 BSs. We finally show that, in addition to a network of liver-specific transcription factors including CCAAT/enhancer-binding protein and hepatocyte nuclear factor 4 alpha, ER might be required for proper Foxa2 function in this tissue.
ISSN: 0888-8809

hal-01357623
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/file/Changes%20in%20gene%20expression%201%20and%20Estrogen%20Receptor_accepted.pdf
DOI : 10.1210/me.2015-1311

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Cell proliferation is a hallmark of cancer and depends on complex signaling networks that are chiefly supported by protein kinase activities. Therapeutic strategies have been used to target specific kinases but new methods are required to identify combined targets and improve treatment. Here, we propose a small interfering RNA genetic screen and an integrative approach to identify kinase networks involved in the proliferation of cancer cells. The functional siRNA screen of 714 kinases in HeLa cells identified 91 kinases implicated in the regulation of cell growth, most of them never being reported in previous whole-genome siRNA screens. Based on gene ontology annotations, we have further discriminated between two classes of kinases that, when suppressed, result in alterations of the mitotic index and provoke cell-cycle arrest. Extinguished kinases that lead to a low mitotic index mostly include kinases implicated in cytosolic signaling. In contrast, extinguished kinases that result in a high mitotic index mostly include kinases implicated in cell division. By mapping hit kinases in the PhosphPOINT phosphoprotein database, we generated scale-free networks consisting of 449 and 661 protein-protein interactions for kinases from low MI and high MI groups, respectively. Further analyses of the kinase interactomes revealed specific modules such as FER- and CRKL-containing modules that connect three members of the epidermal growth factor receptor (EGFR) family, suggesting a tight control of the mitogenic EGF-dependent pathway. Based on experimental studies, we confirm the involvement of these two kinases in the regulation of tumor cell growth. Based on a combined approach of large kinome-wide siRNA screens and ontology annotations, our study identifies for the first time two kinase groups differentially implicated in the control of cell proliferation. We further demonstrate that integrative analysis of the kinase interactome provides key information which can be used to facilitate or optimize target design for new therapeutic strategies. The complete list of protein-protein interactions from the two functional kinase groups will provide a useful database for future investigations.
ISSN: 1471-2164

hal-01118475
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118475
DOI : 10.1186/1471-2164-15-1169
PUBMED : 25540073

Éditeur(s) : HAL CCSD Cold Spring Harbor Laboratory Press
Résumé : “Human and Environmental Genomics” platform (Rennes) for Illumina sequencing / Proteomics Core Facility of the Cambridge Institute (Cancer Research UK)
International audience
Epigenetic mechanisms are believed to play key roles in the establishment of cell-specific transcription programs. Accordingly, the modified bases 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been observed in DNA of genomic regulatory regions such as enhancers, and oxidation of 5mC into 5hmC by Ten-eleven translocation (TET) proteins correlates with enhancer activation. However, the functional relationship between cytosine modifications and the chromatin architecture of enhancers remains elusive. To gain insights into their function, 5mC and 5hmC levels were perturbed by inhibiting DNA methyltransferases and TETs during differentiation of mouse embryonal carcinoma cells into neural progenitors, and chromatin characteristics of enhancers bound by the pioneer transcription factors FOXA1, MEIS1, and PBX1 were interrogated. In a large fraction of the tested enhancers, inhibition of DNA methylation was associated with a significant increase in monomethylation of H3K4, a characteristic mark of enhancer priming. In addition, at some specific enhancers, 5mC oxidation by TETs facilitated chromatin opening, a process that may stabilize MEIS1 binding to these genomic regions.
ISSN: 1088-9051

Droits : http://creativecommons.org/licenses/by-nc/
hal-01533248
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01533248
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01533248/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01533248/file/Genome%20Res.-2017-Mah%C3%A9-947-58.pdf
DOI : 10.1101/gr.211466.116