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Peer Reviewed
See detailElongator depletion causes defective transcript elongation of genes that regulate cell motility
Close, Pierre ULg; Hawkes, N; Cornez, I et al

Poster (2005, November 15)

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See detailElongator drives breast cancer initiation and metastasis formation
Delaunay, Sylvain ULg

Poster (2014, May 08)

Elongator complex functions in diverse cellular processes, such as protein acetylation and tRNA modification, and is essential for cell migration and neuronal differentiation. Although it is well ... [more ▼]

Elongator complex functions in diverse cellular processes, such as protein acetylation and tRNA modification, and is essential for cell migration and neuronal differentiation. Although it is well established that tumor development involves modifications of acetylation-deacetylation dynamics as well as changes in protein translation, the role of Elongator in tumor initiation and invasion remains to be studied. Breast cancer is amongst the most common cause of cancer-related deaths in women, and the majority of them involved metastasis dissemination. In vitro, the inactivation of elongator affects the migration and the clonogenic potential of breast cancer cells. In vivo, expression of the ELP1 and Elp3 subunits is elevated over tumor development and in lung metastasis of PyMT-MMTV breast cancer mice. To address the role of elongator in tumor development in vivo, we generated a mouse model in which the catalytic subunit Elp3 is specifically invalidated in the mammary epithelium (Elp3ΔMEC), that we crossed with the PyMT-MMTV model of breast cancer. Elp3 ablation in the mammary epithelium of the PyMT mice caused a delay in primary tumor initiation and reduced metastasis to distal sites. Moreover, PyMT tumor cells formed less mammospheres in the absence of Elp3. Together, our data demonstrate that elongator complex is a key actor in breast cancer initiation and dissemination. [less ▲]

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See detailElongator orchestrates cerebral cortical neurogenesis
creppe, catherine; malinouskaya, lina; Volvert, Marie-Laure ULg et al

in Medecine Sciences : M/S (2010)

Pas d'abstract pour cette publication

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See detailElongator promotes breast cancer metastasis
Delaunay, Sylvain ULg; Rapino, Francesca ULg; Heukamp, Lukas et al

Poster (2015, March)

Elongator is a protein complex (Elp1-6) involved in diverse cellular processes, such as protein acetylation and tRNA modification and whose function is essential for cell migration and neuronal ... [more ▼]

Elongator is a protein complex (Elp1-6) involved in diverse cellular processes, such as protein acetylation and tRNA modification and whose function is essential for cell migration and neuronal differentiation. Although it is well established that tumor development involves modifications of acetylation-deacetylation dynamics, as well as changes in protein translation, the role of Elongator in tumor initiation and invasion remains to be investigated in vivo. We generated a mouse model in which the Elp3 gene, encoding the catalytic subunit of the complex, is conditionally inactivated in the mammary gland epithelium by using the MMTV-CRE transgenic mouse. The role of Elp3 in tumor development and metastasis formation is then assessed in the PyMT model of invasive breast cancer. [less ▲]

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See detailElongator: an ancestral complex driving transcription and migration through protein acetylation.
Creppe, Catherine ULg; Buschbeck, Marcus

in Journal of biomedicine & biotechnology (2011), 2011

Elongator is an evolutionary highly conserved complex. At least two of its cellular functions rely on the intrinsic lysine acetyl-transferase activity of the elongator complex. Its two known substrates ... [more ▼]

Elongator is an evolutionary highly conserved complex. At least two of its cellular functions rely on the intrinsic lysine acetyl-transferase activity of the elongator complex. Its two known substrates--histone H3 and alpha-tubulin--reflect the different roles of elongator in the cytosol and the nucleus. A picture seems to emerge in which nuclear elongator could regulate the transcriptional elongation of a subset of stress-inducible genes through acetylation of histone H3 in the promoter-distal gene body. In the cytosol, elongator-mediated acetylation of alpha-tubulin contributes to intracellular trafficking and cell migration. Defects in both functions of elongator have been implicated in neurodegenerative disorders. [less ▲]

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See detailElongator: mcm5s2 modification fosters breast cancer metastasis
Delaunay, Sylvain ULg; Rapino, Francesca ULg; Zhou, Zhaoli ULg et al

Scientific conference (2015, March 09)

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the ... [more ▼]

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the wobble U34 base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm5s2-tRNA modification, are upregulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer. Mechanistically, ELP3 and CTU1/2 support cellular invasion through the translation of the oncoprotein DEK. As a result, DEK promotes the IRES-dependent translation of the pro-invasive transcription factor LEF1. Consistently, a DEK mutant, whose codon composition is independent of U34 mcm5s2-tRNA modification, escapes the ELP3- and CTU1- dependent regulation and restores the IRES-dependent LEF1 expression. Our results demonstrate the key role of U34 tRNA modification to support specific translation during breast cancer progression and highlight a functional link between tRNA modification- and IRES-dependent translation during tumor cell invasion and metastasis. [less ▲]

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See detailÉloquence du corps et gymnastique de l’esprit. Le sport et le jeu dans les livres d’emblèmes en France (XVIe-XVIIe siècles)
De Marco, Rosa ULg

in Belmas, Élisabeth; Turcot, Laurent (Eds.) JEUX, SPORTS ET LOISIRS EN FRANCE À L’ÉPOQUE MODERNE (16E-19E SIÈCLES) (in press)

La communication veut aborder le thème du jeu et du sport du point de vue de l'emblème, genre littéraire et artistique en vogue en Europe à partir du XVIe siècle, qui lie le texte et l'image pour exprimer ... [more ▼]

La communication veut aborder le thème du jeu et du sport du point de vue de l'emblème, genre littéraire et artistique en vogue en Europe à partir du XVIe siècle, qui lie le texte et l'image pour exprimer des concepts moraux. Le sport et le jeu mettant en scène dans un espace et un temps déterminés les situations les plus communes de l’existence, offrent au moraliste des riches arguments pour son discours : la victoire, le prix, l’injustice, l’honnêteté, la compétition, la passion, la sociabilité, les vices et les vertus. L’intensité symbolique des représentations de jeu et de sport accrue par le langage emblématique sera soulignée dans la communication afin de comprendre le message politique ou moral ancré à ces activités. Toutefois, il nous est à cœur de comprendre, à travers l’étude de l’emblème, les relations entre le corps et l’esprit telles qui sont perçues au début de l’âge moderne. [less ▲]

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Peer Reviewed
See detailElp3 acetyl-transferase controls neuronal survival in the developing inner ear and is crucial to balance and hearing
Delacroix, Laurence ULg

Conference (2016)

Elp3 lysine acetyl-transferase, the catalytic subunit of the Elongator complex, has been assigned multiple roles in gene transcription, DNA methylation and protein translation efficiency. Given the ... [more ▼]

Elp3 lysine acetyl-transferase, the catalytic subunit of the Elongator complex, has been assigned multiple roles in gene transcription, DNA methylation and protein translation efficiency. Given the importance of acetylation homeostasis in controlling developmental processes together with recent reports implicating Elp3 in cortical neurogenesis, we investigated its role during inner ear formation. In the inner ear, we detected Elp3 transcript in the sensory epithelia of the entire otic vesicle at embryonic day E11.5. At later stages, Elp3 mRNA is strongly expressed in the vestibular and spiral ganglion neurons. To investigate the role of Elp3 in vivo, we used a conditional knock-out mice (Foxg1Cre) in which the expression of the acetyl-transferase is lost in early otocyst. These mice show obvious vestibular defects as indicated by a stereotyped circling ambulation, head bobbing, retropulsion and the absence of a reaching response in the tail-hanging test. Furthermore, we identified a severe hearing loss in Elp3cKO mice through Auditory Brainstem Responses. We show that Elp3 enzyme is crucial for neuronal survival in the spiral ganglion and in the vestibule and that it ensures a correct innervation pattern in the developing inner ear. In the absence of Elp3, a drastic increase in the number of apoptotic neurons was detected by active Caspase-3 and pH2AX immunostainings, particularly during the early stages of development (between E12.5 and E14.5). Postnatally, the neurons remaining in Elp3cKO cochleae seem to establish synaptic contacts with the sensory cells but show obvious signs of cell damage as evidenced by Transmission Electron Microscopy. Taken together, these data support a role for Elp3 in hearing and balance and point out an important role for acetylation homeostasis during inner ear formation. We are currently investigating the molecular mechanisms underlying Elp3 effect on neuronal survival and pathfinding. [less ▲]

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See detailElp3 drives Wnt-dependent tumor initiation and regeneration in the intestine
LADANG, Aurélie ULg; Rapino, Francesca ULg; Heukamp, Lukas et al

in Journal of Experimental Medicine (2015), 212(12), 2057-75

Tumor initiation in the intestine can rapidly occur from Lgr5(+) crypt columnar stem cells. Dclk1 is a marker of differentiated Tuft cells and, when coexpressed with Lgr5, also marks intestinal cancer ... [more ▼]

Tumor initiation in the intestine can rapidly occur from Lgr5(+) crypt columnar stem cells. Dclk1 is a marker of differentiated Tuft cells and, when coexpressed with Lgr5, also marks intestinal cancer stem cells. Here, we show that Elp3, the catalytic subunit of the Elongator complex, is required for Wnt-driven intestinal tumor initiation and radiation-induced regeneration by maintaining a subpool of Lgr5(+)/Dclk1(+)/Sox9(+) cells. Elp3 deficiency dramatically delayed tumor appearance in Apc-mutated intestinal epithelia and greatly prolonged mice survival without affecting the normal epithelium. Specific ablation of Elp3 in Lgr5(+) cells resulted in marked reduction of polyp formation upon Apc inactivation, in part due to a decreased number of Lgr5(+)/Dclk1(+)/Sox9(+) cells. Mechanistically, Elp3 is induced by Wnt signaling and promotes Sox9 translation, which is needed to maintain the subpool of Lgr5(+)/Dclk1(+) cancer stem cells. Consequently, Elp3 or Sox9 depletion led to similar defects in Dclk1(+) cancer stem cells in ex vivo organoids. Finally, Elp3 deficiency strongly impaired radiation-induced intestinal regeneration, in part because of decreased Sox9 protein levels. Together, our data demonstrate the crucial role of Elp3 in maintaining a subpopulation of Lgr5-derived and Sox9-expressing cells needed to trigger Wnt-driven tumor initiation in the intestine. [less ▲]

Detailed reference viewed: 116 (36 ULg)
Peer Reviewed
See detailElp3 is required for initiation of colon cancer
Ladang, Aurélie ULg; Heukamp, L; Buettner, R et al

Poster (2013, September 18)

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See detailELP3 links tRNA modification to IRES-dependent translation of LEF-1 to promote metastasis in breast cancer
Delaunay, Sylvain ULg; Rapino, Francesca ULg; Tharun, Lars et al

in The Journal of Experimental Medicine (2016), 213

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the ... [more ▼]

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the wobble U34 base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm5s2-tRNA modification, are upregulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer. Mechanistically, ELP3 and CTU1/2 support cellular invasion through the translation of the oncoprotein DEK. As a result, DEK promotes the IRES-dependent translation of the pro-invasive transcription factor LEF1. Consistently, a DEK mutant, whose codon composition is independent of U34 mcm5s2-tRNA modification, escapes the ELP3- and CTU1-dependent regulation and restores the IRES-dependent LEF1 expression. Our results demonstrate the key role of U34 tRNA modification to support specific translation during breast cancer progression and highlight a functional link between tRNA modification- and IRES-dependent translation during tumor cell invasion and metastasis. [less ▲]

Detailed reference viewed: 18 (3 ULg)
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See detailElp3 Lysine Acetyl-Transferase Controls Neuronal Survival in the Developing Inner Ear and is Crucial to Balance and Hearing
Delacroix, Laurence ULg; Mateo Sanchez, Susana ULg; Freeman, Stephen ULg et al

Conference (2016, February 20)

Elp3 lysine acetyl-transferase, the catalytic subunit of the Elongator complex, has been assigned multiple roles in gene transcription, DNA methylation and protein translation efficiency. Given the ... [more ▼]

Elp3 lysine acetyl-transferase, the catalytic subunit of the Elongator complex, has been assigned multiple roles in gene transcription, DNA methylation and protein translation efficiency. Given the importance of acetylation homeostasis in controlling developmental processes together with recent reports implicating Elp3 in cortical neurogenesis, we investigated its role during inner ear formation. In the inner ear, we detected Elp3 transcript in the sensory epithelia of the entire otic vesicle at embryonic day E11.5. At later stages, Elp3 mRNA is strongly expressed in the vestibular and spiral ganglion neurons. To investigate the role of Elp3 in vivo, we used a conditional knock-out mice (Foxg1Cre) in which the expression of the acetyl-transferase is lost in early otocyst. These mice show obvious vestibular defects as indicated by a stereotyped circling ambulation, head bobbing, retropulsion and the absence of a reaching response in the tail-hanging test. Furthermore, we identified a severe hearing loss in Elp3cKO mice through Auditory Brainstem Responses. We show that Elp3 enzyme is crucial for neuronal survival in the spiral ganglion and in the vestibule and that it ensures a correct innervation pattern in the developing inner ear. In the absence of Elp3, a drastic increase in the number of apoptotic neurons was detected by active Caspase-3 and pH2AX immunostainings, particularly during the early stages of development (between E12.5 and E14.5). Postnatally, the neurons remaining in Elp3cKO cochleae seem to establish synaptic contacts with the sensory cells but show obvious signs of cell damage as evidenced by Transmission Electron Microscopy. Taken together, these data support a role for Elp3 in hearing and balance and point out an important role for acetylation homeostasis during inner ear formation. We are currently investigating the molecular mechanisms underlying Elp3 effect on neuronal survival and pathfinding. [less ▲]

Detailed reference viewed: 56 (17 ULg)
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See detailEls problemes de la violència esportiva. 10 anys després de Heysel
Comeron, Manuel ULg; Van Limbergen, Kris

in Revista d’Historia L'Avenç (1997), (211), 25-32

Les conductes violentes desenvolupades pels seguidors de futbol, tradicionalment anomenades hooliganismo, estan profundament arrelades en la historia i tenen una difusio geografica molt amplia, es ... [more ▼]

Les conductes violentes desenvolupades pels seguidors de futbol, tradicionalment anomenades hooliganismo, estan profundament arrelades en la historia i tenen una difusio geografica molt amplia, es relaciona llavors amb comportaments d'agressio fisica i de vandalisme produïts pels espectadors d'una manifestacio esportiva, mes concretament dels partits de futbol. [less ▲]

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See detailEls Terratrèmols de l'any 1373 al Pirineu : Efectes a Espanya i França
Olivera, Carme; Riera, Antoni; Alexandre, Pierre ULg et al

Book published by Servei Geologic de Catalunya (1994)

Detailed reference viewed: 44 (0 ULg)
See detailElucidating diversity of thin filamentous mat-forming Antarctic cyanobacteria
Lara, Yannick ULg; Durieu, Benoit ULg; Deblander, Victor ULg et al

Poster (2016, April 29)

Freshwater ecosystems range from glacial cryoecosystems, ice shelf meltwater ponds to perennially ice-covered lakes where conspicuous benthic microbial mat communities constitute most of the biomass. In ... [more ▼]

Freshwater ecosystems range from glacial cryoecosystems, ice shelf meltwater ponds to perennially ice-covered lakes where conspicuous benthic microbial mat communities constitute most of the biomass. In these mats, cyanobacteria form matrices that shelter other organisms, and carry out the primary production. Narrow filamentous cyanobacteria belonging to the genera Leptolyngbya and Phormidium are especially abundant in Antarctic microbial mats and are essential for the formation of matrix. However, the lack of morphological criteria and the small cell size of cyanobacteria belonging to these two genera make their identification problematic. Indeed, they are known as polyphyletic taxa according to botanical and bacteriological criteria. The characterization of strains is the first step for an assessment of the real diversity and for understanding their role in the environment. We designed a polyphasic approach that combines molecular analyses, environmental physiology experiments and microscopic observations. Briefly, we amplified and sequenced three loci (16S rRNA, ITS, and rpoC1) for 31 strains of Leptolyngbya and Phormidium. We performed whole genome sequencing for five strains. Cultures at different stage were observed by light and epifluorescence microscopy. Finally, selected strains were grown in nitrogen-limited. The Leptolyngbya and Phormidium strains were distributed into four lineages. Phylogenetic trees supported the distribution of P. priestleyi strains into at least two potentially new lineages, and L. antarctica strains were separated into one endemic and one cosmopolitan lineage. This was supported by the microscopic observations of 1-year old cultures. Genome analyses revealed the presence of sequences related to the production of secondary metabolites in strains from two of the studied lineages. Secondary metabolites are often known for their antimicrobial activities. Such properties would partly explain how cyanobacterial mats survive to predation and degradation by other bacteria. This work provides the first building block to the understanding of survival strategies developed by mat-forming cyanobacteria and how they succeeded as the most abundant phototrophs on the Antarctic continent. This work was realized in the frame of the BelSPo project CCAMBIO. [less ▲]

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See detailElucidating the altered transcriptional programs in breast cancer using independent component analysis
Teschendorff, A. E.; Journee, Michel ULg; Absil, P.-A. et al

in PLoS Computational Biology (2007), 3(8), 1539-1554

The quantity of mRNA transcripts in a cell is determined by a complex interplay of cooperative and counteracting biological processes. Independent Component Analysis ( ICA) is one of a few number of ... [more ▼]

The quantity of mRNA transcripts in a cell is determined by a complex interplay of cooperative and counteracting biological processes. Independent Component Analysis ( ICA) is one of a few number of unsupervised algorithms that have been applied to microarray gene expression data in an attempt to understand phenotype differences in terms of changes in the activation/ inhibition patterns of biological pathways. While the ICA model has been shown to outperform other linear representations of the data such as Principal Components Analysis ( PCA), a validation using explicit pathway and regulatory element information has not yet been performed. We apply a range of popular ICA algorithms to six of the largest microarray cancer datasets and use pathway- knowledge and regulatory- element databases for validation. We show that ICA outperforms PCA and clustering- based methods in that ICA components map closer to known cancer- related pathways, regulatory modules, and cancer phenotypes. Furthermore, we identify cancer signalling and oncogenic pathways and regulatory modules that play a prominent role in breast cancer and relate the differential activation patterns of these to breast cancer phenotypes. Importantly, we find novel associations linking immune response and epithelial - mesenchymal transition pathways with estrogen receptor status and histological grade, respectively. In addition, we find associations linking the activity levels of biological pathways and transcription factors ( NF1 and NFAT) with clinical outcome in breast cancer. ICA provides a framework for a more biologically relevant interpretation of genomewide transcriptomic data. Adopting ICA as the analysis tool of choice will help understand the phenotype - pathway relationship and thus help elucidate the molecular taxonomy of heterogeneous cancers and of other complex genetic diseases. [less ▲]

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See detailElucidating the opto-electrical properties of solid and hollow titania scattering layers for improvement of dye-sensitized solar cells
Thalluri, Venkata Visveswara Gopala Kris; Henrist, Catherine ULg; Spronck, Gilles ULg et al

in Thin Solid Films (2015)

The light scattering method has been adapted in dye-sensitized solar cells (DSCs) for optical absorption enhancement. In DSC's, particle-size of TiO2 should be inline with the scattering wavelength range ... [more ▼]

The light scattering method has been adapted in dye-sensitized solar cells (DSCs) for optical absorption enhancement. In DSC's, particle-size of TiO2 should be inline with the scattering wavelength range. Scattering particles can be used either by forming a bilayer structure with TiO2 nanocrystalline film or into the bulk of TiO2 nanocrystalline film. For improving the DSCs performances these scattering layers aim to refract/reflect the incident light by extending the traveling distance of UV-Visible/near-IR light within the dye-sensitized TiO2 nanocrystalline film. In this work, the scattering layers with two different particle-sizes (~200 nm-solid and ~400 nm-hollow) were deposited as an additional layer on the top of dye-sensitized TiO2 nanocrystalline film and the morphological properties were studied. By using various opto-electrical characterization techniques, the influence of these scattering layers for two different classes of DSCs prepared from N3 (UV-Vis) and SQ2 (near-IR) dyes were investigated. [less ▲]

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See detailElucidating the role of Bovine Leukemia Virus encoded micro-RNAs
Durkin, Keith ULg; Rosewick, Nicolas; Momont, Momont et al

in Retrovirology (2014, January 07), 11(1), 62

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See detailElucidating the structure of genetic regulatory networks: a study of a second order dynamical model on artificial data
Quach, Minh; Geurts, Pierre ULg; d Alché-Buc, Florence

in Proc. of the 14th European Symposium on Artificial Neural Networks (2006)

Learning regulatory networks from time-series of gene expres- sion is a challenging task. We propose to use synthetic data to analyze the ability of a state-space model to retrieve the network structure ... [more ▼]

Learning regulatory networks from time-series of gene expres- sion is a challenging task. We propose to use synthetic data to analyze the ability of a state-space model to retrieve the network structure while varying a number of relevant problem parameters. ROC curves together with new tools such as spectral clustering of local solutions found by EM are used to analyze these results and provide relevant insights. [less ▲]

Detailed reference viewed: 19 (1 ULg)