Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire

Saint-Étienne-de-Baïgorry, France

Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire

Saint-Étienne-de-Baïgorry, France

Time filter

Source Type

Pastore A.,UK National Institute for Medical Research | Puccio H.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Puccio H.,French Institute of Health and Medical Research | Puccio H.,University of Strasbourg | Puccio H.,Collège de France
Journal of Neurochemistry | Year: 2013

Reduced levels of the protein frataxin cause the neurodegenerative disease Friedreich's ataxia. Pathology is associated with disruption of iron-sulfur cluster biosynthesis, mitochondrial iron overload, and oxidative stress. Frataxin is a highly conserved iron-binding protein present in most organisms. Despite the intense interest generated since the determination of its pathology, identification of the cellular function of frataxin has so far remained elusive. In this review, we revisit the most significant milestones that have led us to our current understanding of frataxin and its functions. The picture that emerges is that frataxin is a crucial element of one of the most essential cellular machines specialized in iron-sulfur cluster biogenesis. Future developments, therefore, can be expected from further advancements in our comprehension of this machine. © 2013 International Society for Neurochemistry.

Herquel B.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire
Transcription | Year: 2011

TRIM24 (TIF1α), TRIM28 (TIF1β) and TRIM33 (TIF1γ) are related cofactors defining a subgroup of the tripartite motif (TRIM) superfamily comprising an N-terminal RING finger E3 ligase and a C-terminal PHD-Bromodomain chromatin interacting module. Increasing evidence highlights the important roles of these proteins as modulators of multiple signaling pathways during normal development and as tumor suppressors. The finding that they interact to form a multiprotein complex suggests new mechanisms to integrate multiple signaling pathways for tumor suppression.

Shankaranarayanan P.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Mendoza-Parra M.-A.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Van Gool W.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Trindade L.M.,Wageningen University | Gronemeyer H.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire
Nature Protocols | Year: 2012

Linear amplification of DNA (LinDA) by T7 polymerase is a versatile and robust method for generating sufficient amounts of DNA for genome-wide studies with minute amounts of cells. LinDA can be coupled to a great number of global profiling technologies. Indeed, chromatin immunoprecipitation coupled to massive parallel sequencing (ChIP-seq) has been achieved for transcription factors and epigenetic modification of chromatin histones with 1,000 to 5,000 cells. LinDA largely simplifies reChIP-seq experiments to monitor co-binding at chromatin target sites. The single-tube design of LinDA is ideal for handling ultrasmall amounts of DNA (<30 pg) and is compatible with automation. The actual hands-on working time is less than 6 h with one overnight reaction. The present protocol describes all materials and critical steps, and provides examples and controls for LinDA. Applications of LinDA for genome-wide analyses of biobank samples and for the study of chromatin conformation and nuclear architecture are in progress. © 2012 Nature America, Inc. All rights reserved.

Le Merrer J.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Rezai X.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Rezai X.,University of Lausanne | Scherrer G.,Stanford University | And 2 more authors.
Neuropsychopharmacology | Year: 2013

Pharmacological data suggest that delta opioid receptors modulate learning and memory processes. In the present study, we investigated whether inactivation of the delta opioid receptor modifies hippocampus (HPC)-and striatum-dependent behaviors. We first assessed HPC-dependent learning in mice lacking the receptor (Oprd1-/-mice) or wild-type (WT) mice treated with the delta opioid antagonist naltrindole using novel object recognition, and a dual-solution cross-maze task. Second, we subjected mutant animals to memory tests addressing striatum-dependent learning using a single-solution response cross-maze task and a motor skill-learning task. Genetic and pharmacological inactivation of delta opioid receptors reduced performance in HPC-dependent object place recognition. Place learning was also altered in Oprd1-/-animals, whereas striatum-dependent response and procedural learning were facilitated. Third, we investigated the expression levels for a large set of genes involved in neurotransmission in both HPC and striatum of Oprd1-/-mice. Gene expression was modified for several key genes that may contribute to alter hippocampal and striatal functions, and bias striatal output towards striatonigral activity. To test this hypothesis, we finally examined locomotor effects of dopamine receptor agonists. We found that Oprd1-/-and naltrindole-treated WT mice were more sensitive to the stimulant locomotor effect of SKF-81297 (D1/D5), supporting the hypothesis of facilitated striatonigral output. These data suggest, for the first time, that delta receptor activity tonically inhibits striatal function, and demonstrate that delta opioid receptors modulate learning and memory performance by regulating the HPC/striatum balance. © 2013 American College of Neuropsychopharmacology.

Wicker N.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire
Statistics and Computing | Year: 2010

A Markov chain is proposed that uses coupling from the past sampling algorithm for sampling m × n contingency tables. This method is an extension of the one proposed by Kijima and Matsui (Rand. Struct. Alg., 29:243-256, 2006). It is not polynomial, as it is based upon a recursion, and includes a rejection phase but can be used for practical purposes on small contingency tables as illustrated in a classical 4×4 example. © Springer Science+Business Media, LLC 2009.

Camand E.,Institute Pasteur Paris | Peglion F.,Institute Pasteur Paris | Osmani N.,Institute Pasteur Paris | Osmani N.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | And 2 more authors.
Journal of Cell Science | Year: 2012

Perturbation of cell polarity is a hallmark of cancer cells. In carcinomas, loss of epithelial E-cadherin contributes to the loss of cell polarity and promotes epithelial-mesenchymal transition and carcinoma infiltration. However, the contribution of classical cadherins to the development of non-epithelial tumours is less well documented. We investigated the impact of the level of N-cadherin expression on the polarity and migration of normal and tumour glial cells. Low levels of N-cadherin were frequently observed in human glioma samples and purified glioma cells. Using a wound-healing assay, we show that a decreased level of N-cadherin promotes a faster and less-directed migration both in normal and tumour cells. N-cadherin-mediated contacts control cell velocity and polarity through the regulation of focal adhesions. In cells expressing low levels of N-cadherin, small focal adhesions are present at the entire cell periphery of confluent cells and are not affected by wounding of the cell monolayer. Under these conditions, wound-induced integrin-mediated recruitment of the small GTPase Cdc42, activation of the Cdc42-mediated polarity pathway and centrosome reorientation do not occur. Re-expression of N-cadherin in gliomas restores cell polarity and strongly reduces cell velocity, suggesting that loss of N-cadherin could contribute to the invasive capacity of tumour astrocytes. © 2012.

Canto C.,Ecole Polytechnique Federale de Lausanne | Jiang L.Q.,Karolinska Institutet | Deshmukh A.S.,Karolinska Institutet | Mataki C.,Ecole Polytechnique Federale de Lausanne | And 4 more authors.
Cell Metabolism | Year: 2010

During fasting and after exercise, skeletal muscle efficiently switches from carbohydrate to lipid as the main energy source to preserve glycogen stores and blood glucose levels for glucose-dependent tissues. Skeletal muscle cells sense this limitation in glucose availability and transform this information into transcriptional and metabolic adaptations. Here we demonstrate that AMPK acts as the prime initial sensor that translates this information into SIRT1-dependent deacetylation of the transcriptional regulators PGC-1α and FOXO1, culminating in the transcriptional modulation of mitochondrial and lipid utilization genes. Deficient AMPK activity compromises SIRT1-dependent responses to exercise and fasting, resulting in impaired PGC-1α deacetylation and blunted induction of mitochondrial gene expression. Thus, we conclude that AMPK acts as the primordial trigger for fasting- and exercise-induced adaptations in skeletal muscle and that activation of SIRT1 and its downstream signaling pathways are improperly triggered in AMPK-deficient states. © 2010 Elsevier Inc. All rights reserved.

Jenner L.B.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Jenner L.B.,French Institute of Health and Medical Research | Demeshkina N.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Demeshkina N.,French National Center for Scientific Research | And 4 more authors.
Nature Structural and Molecular Biology | Year: 2010

One key question in protein biosynthesis is how the ribosome couples mRNA and tRNA movements to prevent disruption of weak codon-anticodon interactions and loss of the translational reading frame during translocation. Here we report the complete path of mRNA on the 70S ribosome at the atomic level (3.1-resolution), and we show that one of the conformational rearrangements that occurs upon transition from initiation to elongation is a narrowing of the downstream mRNA tunnel. This rearrangement triggers formation of a network of interactions between the mRNA downstream of the A-site codon and the elongating ribosome. Our data elucidate the mechanism by which hypermodified nucleoside 2-methylthio-N6 isopentenyl adenosine at position 37 (ms 2 i 6 A37) in tRNA Phe GAA stabilizes mRNA-tRNA interactions in all three tRNA binding sites. Another network of contacts is formed between this tRNA modification and ribosomal elements surrounding the mRNA E/P kink, resulting in the anchoring of P-site tRNA. These data allow rationalization of how modification deficiencies of ms 2 i 6 A37 in tRNAs may lead to shifts of the translational reading frame. © 2010 Nature America, Inc. All rights reserved.

Gavriilidis C.,Northumbria University | Gavriilidis C.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Miwa S.,Northumbria University | Von Zglinicki T.,Northumbria University | And 2 more authors.
Arthritis and Rheumatism | Year: 2013

Objective Superoxide dismutase 2 (SOD2) is down- regulated in osteoarthritis (OA). This study was undertaken to investigate the functional effects of this down-regulation in the context of oxidative damage and mitochondrial dysfunction. Methods Lipid peroxidation in articular cartilage from OA patients and from lesion-free control subjects with femoral neck fracture was assessed by measuring malondialdehyde levels using the thiobarbituric acid reactive substances assay. Long-range polymerase chain reaction amplification and a mitochondrial DNA (mtDNA) strand break assay were used to investigate the presence of somatic large-scale mtDNA rearrangements in cartilage. Microscale oxygraphy was used to explore possible changes in mitochondrial respiratory activity between OA and control chondrocytes. RNA interference was used to determine the effects of SOD2 depletion on lipid peroxidation, mtDNA damage, and mitochondrial respiration. Results OA cartilage had higher levels of lipid peroxidation compared to control cartilage, and lipid peroxidation was similarly elevated in SOD2-depleted chondrocytes. SOD2 depletion led to a significant increase in mtDNA strand breaks in chondrocytes, but there was no notable difference in the level of strand breaks between OA and control chondrocytes. Furthermore, only very low levels of somatic, large-scale mtDNA rearrangements were identified in OA cartilage. OA chondrocytes showed less spare respiratory capacity (SRC) and higher proton leak compared to control chondrocytes. SOD2-depleted chondrocytes also showed less SRC and higher proton leak. Conclusion This is the first study to analyze the effects of SOD2 depletion in human articular chondrocytes in terms of changes to oxidation and mitochondrial function. The findings indicate that SOD2 depletion in chondrocytes leads to oxidative damage and mitochondrial dysfunction, suggesting that SOD2 down-regulation is a potential contributor to the pathogenesis of OA. Copyright © 2013 by the American College of Rheumatology.

Fehrmann S.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Paoletti C.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Goulev Y.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Ungureanu A.,LJC | And 2 more authors.
Cell Reports | Year: 2013

In budding yeast, a mother cell can produce a finite number of daughter cells before it stops dividing and dies. Such entry into senescence is thought to result from a progressive decline in physiological function, including a loss of mitochondrial membrane potential (δΨ). Here, we developed a microfluidic device to monitor the dynamics of cell division and δΨ in real time at single-cell resolution. We show that cells do not enter senescence gradually but rather undergo an abrupt transition to a slowly dividing state. Moreover, we demonstrate that the decline in δΨ, which is observed only in a fraction of cells, is not responsible for entry into senescence. Rather, the loss of δΨ is an age-independent and heritable process that leads to clonal senescence and is therefore incompatible with daughter cell rejuvenation. These results emphasize the importance of quantitative single-cell measurements to decipher the causes of cellular aging. © 2013 The Authors.

Loading Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire collaborators
Loading Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire collaborators