Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generation males. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations.
ISSN: 0305-1048

hal-01477213
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477213
DOI : 10.1093/nar/gkw840
PUBMED : 27655631

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

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Voltage-gated calcium currents are important for the survival and growth of embryonic cockroach brain neurons in primary culture. In the present experiments, we have studied, using the patch-clamp technique, the evolution with time in culture of the voltage-dependency and of the pharmacological properties of the calcium conductance of these neurons during the formation of a network. We have observed a progressive increase of the high-voltage-activated calcium conductance and a 10mV shift of the voltage-dependency of activation towards more negative potentials. The proportion of the R-like calcium current component increased during network formation. At the same time, the highly omega-AgaTxIVA-sensitive P-like component of the current is progressively replaced by a component which is less sensitive to the toxin. The origin and functional implications of these modifications are discussed.
ISSN: 0304-3940

hal-00982273
https://hal.archives-ouvertes.fr/hal-00982273
DOI : 10.1016/j.neulet.2004.05.002
PUBMED : 15246554

Éditeur(s) : HAL CCSD
Résumé : International audience
Ctenophores are non-bilaterian metazoans of uncertain phylogenetic position, some recent studies placing them as sister-group to all other animals whereas others suggest this placement is artefactual and ctenophores are more closely allied with cnidarians and bilaterians, with which they share nerve cells, muscles and gut. Available information about developmental genes and their expression and function in ctenophores is reviewed. These data not only unveil some conserved aspects of molecular developmental mechanisms with other basal metazoan lineages, but also can be expected to enlighten the genomic and molecular bases of the evolution of ctenophore-specific traits, including their unique embryonic development, complex anatomy and high cell type diversity.
ISSN: 0959437X

hal-01509720
http://hal.upmc.fr/hal-01509720
ARXIV : 1605.05876
DOI : 10.1016/j.gde.2016.05.020

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The Ras/Raf/MEK/ERK signaling pathway is involved in essential cell processes and it is abnormally activated in similar to 30 % of cancers and cognitive disorders. Two ERK isoforms have been described, ERK1 and ERK2; ERK2 being regarded by many as essential due to the embryonic lethality of ERK2 knock-out mice, whereas mice lacking ERK1 are viable and fertile. The controversial question of why we have two ERKs and whether they have differential functions or display functional redundancy has not yet been resolved. Results: To investigate this question we used a novel approach based on comparing the evolution of ERK isoforms' sequences and protein expression across vertebrates. We gathered and cloned erk1 and erk2 coding sequences and we examined protein expression of isoforms in brain extracts in all major clades of vertebrate evolution. For the first time, we measured each isoforms' relative protein level in phylogenetically distant animals using anti-phospho antibodies targeting active ERKs. We demonstrate that squamates (lizards, snakes and geckos), despite having both genes, do not express ERK2 protein whereas other tetrapods either do not express ERK1 protein or have lost the erk1 gene. To demonstrate the unexpected squamates' lack of ERK2 expression, we targeted each ERK isoform in lizard primary fibroblasts by specific siRNA-mediated knockdown. We also found that undetectable expression of ERK2 in lizard is compensated by a greater strength of lizard's erk1 promoter. Finally, phylogenetic analysis revealed that ERK1 amino acids sequences evolve faster than ERK2' s likely due to genomic factors, including a large difference in gene size, rather than from functional differences since amino acids essential for function are kept invariant. Conclusions: ERK isoforms appeared by a single gene duplication at the onset of vertebrate evolution at least 400 Mya. Our results demonstrate that tetrapods can live by expressing either one or both ERK isoforms, supporting the notion that ERK1/2 act interchangeably. Substrate recognition sites and catalytic cleft are nearly invariant in all vertebrate ERKs further suggesting functional redundancy. We suggest that future ERK research should shift towards understanding the role and regulation of total ERK quantity, especially in light of newly described erk2 gene amplification identified in tumors.
ISSN: 1471-2148

hal-01546165
https://hal.archives-ouvertes.fr/hal-01546165
DOI : 10.1186/s12862-015-0450-x

Éditeur(s) : HAL CCSD Station Biologique
Résumé : International audience
The embryonic development of Tivela mactroides, from fertilization to straight-hinge veliger D-stage larva occurs in 18 hours at 25°C. Scanning electronic observations show that morphogenetic processes result in a gastrula with two depressions 4 hours after fertilization (T0 + 4h). Two hours later, one depression, located at the animal pole, develops into an open cave, the floor of which becomes the shell field located below the lower face of the prototrochal pad. The invagination located at the vegetal pole features the blastopore. At T0 + 6h, the late gastrula has differentiated into a typical motile trochophore with a shell field synthetizing the organic part of the shell. At T0 + 8h, the shell field, located between the prototroch and the telotroch, appears as a saddle-shaped region with a wrinkled surface extending on both sides of the embryo, establishing bilateral symmetry. At T0 + 12h, the prototroch slides toward the anterior region by outgrowth of the shell material. At T0 + 18h, the prodissoconch I formation is completed and the D-stage larvae possess a calcified shell. At this stage of development, the functional velum is composed of four bands of cilia. Our observations seem to confirm the interpretation of shell differentiation proposed recently by Mouëza et al. (2006) for bivalves even if Transmission Electronic observations will be necessary to validate definitively such a model in the Meretricinae sub-family.
ISSN: 0007-9723

hal-00753022
https://hal.univ-antilles.fr/hal-00753022

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
AbstractThis review provides a global overview of microporous silica based membranes for desalination via pervaporation with a focus on membrane synthesis and processing, transport mechanisms and current state of the art membrane performance. Most importantly, the recent development and novel concepts for improving the hydro-stability and separating performance of silica membranes for desalination are critically examined. Research into silica based membranes for desalination has focussed on three primary methods for improving the hydro-stability. These include incorporating carbon templates into the microporous silica both as surfactants and hybrid organic-inorganic structures and incorporation of metal oxide nanoparticles into the silica matrix. The literature examined identified that only metal oxide silica membranes have demonstrated high salt rejections under a variety of feed concentrations, reasonable fluxes and unaltered performance over long-term operation. As this is an embryonic field of research several target areas for researchers were discussed including further improvement of the membrane materials, but also regarding the necessity of integrating waste or solar heat sources into the final process design to ensure cost competitiveness with conventional reverse osmosis processes. © 2012 by the authors.
ISSN: 2073-4441

hal-01683200
https://hal.univ-antilles.fr/hal-01683200
DOI : 10.3390/w4030629

Éditeur(s) : HAL CCSD
Résumé : International audience
ISSN: 1875-2535

hal-01084493
https://hal-agroparistech.archives-ouvertes.fr/hal-01084493
DOI : 10.1163/187525409X462412

Éditeur(s) : HAL CCSD Royal Society
Résumé : International audience
Maternal Embryonic Leucine zipper Kinase (MELK) was recently shown to be involved in cell division of Xenopus embryo epithelial cells. The cytokinetic furrow of these cells ingresses asymmetrically and is developmentally regulated. Two subpopulations of xMELK, the mMELK (for "mitotic" xMELK) and iMELK ("interphase" xMELK), which differ in their spatial and temporal regulation, are detected in Xenopus embryo. How cells regulate these two xMELK populations is unknown. In this study we show that, in epithelial cells, xMELK is present at a higher concentration at the apical junctional complex, in contrast to mesenchyme-like cells, which have uniform distribution of cortical MELK. Interestingly, mMELK and iMELK also differ by their requirements towards cell-cell contacts to establish their proper cortical localization both in epithelial and mesenchyme-like cells. Receptor for Activated protein Kinase C (RACK1), which we identified as an xMELK partner, co-localizes with xMELK at the tight junction. Moreover, a truncated RACK1 construct interferes with iMELK localization at cell-cell contacts. Collectively, our results suggest that iMELK and RACK1 are present in the same complex and that RACK1 is involved in the specific recruitment of iMELK at the apical junctional complex in epithelial cells of Xenopus embryos.
ISSN: 2046-6390

hal-00874053
https://hal.archives-ouvertes.fr/hal-00874053
https://hal.archives-ouvertes.fr/hal-00874053/document
https://hal.archives-ouvertes.fr/hal-00874053/file/Cell-cycle_dependent-accepted.pdf
DOI : 10.1242/bio.20136080

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Chaperone synthesis in response to proteotoxic stress is dependent on a family of transcription factors named heat shock factors (HSFs). The two main factors in this family, HSF1 and HSF2, are co-expressed in numerous tissues where they can interact and form heterotrimers in response to proteasome inhibition. HSF1 and HSF2 exhibit two alternative splicing isoforms, called α and β, which contribute to additional complexity in HSF transcriptional regulation, but remain poorly examined in the literature. In this work, we studied the transcriptional activity of HSF1 and HSF2 splicing isoforms transfected into immortalized Mouse Embryonic Fibroblasts (iMEFs) deleted for both Hsf1 and Hsf2, under normal conditions and after proteasome inhibition. We found that HSF1α is significantly more active than the β isoform after exposure to the proteasome inhibitor MG132. Furthermore, we clearly established that, while HSF2 had no transcriptional activity by itself, short β isoform of HSF2 exerts a negative role on HSF1β-dependent transactivation. To further assess the impact of HSF2β inhibition on HSF1 activity, we developed a mathematical modelling approach which revealed that the balance between each HSF isoform in the cell regulated the strength of the transcriptional response. Moreover, we found that cellular stress such as proteasome inhibition could regulate the splicing of Hsf2 mRNA. All together, our results suggest that relative amounts of each HSF1 and HSF2 isoforms quantitatively determine the cellular level of the proteotoxic stress response.
ISSN: 1932-6203

inserm-00814784
http://www.hal.inserm.fr/inserm-00814784
http://www.hal.inserm.fr/inserm-00814784/document
http://www.hal.inserm.fr/inserm-00814784/file/journal.pone.0056085.pdf
DOI : 10.1371/journal.pone.0056085

Éditeur(s) : HAL CCSD National Academy of Sciences
Résumé : International audience
Stem cells are pivotal for development and tissue homeostasis of multicellular animals, and the quest for a gene toolkit associated with the emergence of stem cells in a common ancestor of all metazoans remains a major challenge for evolutionary biology. We reconstructed the conserved gene repertoire of animal stem cells by transcriptomic profiling of totipotent archeocytes in the demosponge Ephydatia fluviatilis and by tracing shared molecular signatures with flatworm and Hydra stem cells. Phylostratigraphy analyses indicated that most of these stem-cell genes predate animal origin, with only few metazoan innovations, notably including several partners of the Piwi machinery known to promote genome stability. The ancestral stem-cell transcriptome is strikingly poor in transcription factors. Instead, it is rich in RNA regulatory actors, including components of the ``germ-line multipotency program'' and many RNA-binding proteins known as critical regulators of mammalian embryonic stem cells.
ISSN: 0027-8424

hal-01544480
https://hal.archives-ouvertes.fr/hal-01544480
DOI : 10.1073/pnas.1514789112