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Comino-Mendez I.,Hereditary Endocrine Cancer Group | Tejera A.M.,Telomeres and Telomerase Group | Curras-Freixes M.,Hereditary Endocrine Cancer Group | Remacha L.,Hereditary Endocrine Cancer Group | And 9 more authors.
Cancer Genetics

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are tumors arising from the adrenal medulla and sympathetic/parasympathetic paraganglia, respectively. Approximately 40% of PCCs/PGLs are due to germline mutations in one of 16 susceptibility genes, and a further 30% are due to somatic alterations in 5 main genes. Recently, somatic ATRX mutations have been found in succinate dehydrogenase (SDH)-associated hereditary PCCs/PGLs. In the present study we applied whole-exome sequencing to the germline and tumor DNA of a patient with metastatic composite PCC and no alterations in known PCC/PGL susceptibility genes. A somatic loss-of-function mutation affecting ATRX was identified in tumor DNA. Transcriptional profiling analysis classified the tumor within cluster 2 of PCCs/PGLs (without SDH gene mutations) and identified downregulation of genes involved in neuronal development and homeostasis (NLGN4, CD99 and CSF2RA) as well as upregulation of Drosha, an important gene involved in miRNA and rRNA processing. CpG island methylator phenotype typical of SDH gene-mutated tumors was ruled out, and SNP array data revealed a unique profile of gains and losses. Finally, we demonstrated the presence of alternative lengthening of telomeres in the tumor, probably associated with the failure of ATRX functions. In conclusion, somatic variants affecting ATRX may play a driver role in sporadic PCC/PGL. © 2016 Elsevier Inc. Source

Belton J.-M.,University of Massachusetts Medical School | Lajoie B.R.,University of Massachusetts Medical School | Audibert S.,Toulouse 1 University Capitole | Audibert S.,French National Center for Scientific Research | And 14 more authors.
Cell Reports

Mating-type switching in yeast occurs through gene conversion between the MAT locus and one of two silent loci (HML or HMR) on opposite ends of the chromosome. MATa cells choose HML as template, whereas MATα cells use HMR. The recombinationenhancer (RE) located on the left arm regulates thisprocess. One long-standing hypothesis is that switching is guided by mating-type-specific and possibly RE-dependent chromosome folding. Here, we use Hi-C, 5C, and live-cell imaging to characterize the conformation of chromosome III in both mating types. We discovered a mating-type-specific conformational difference in the left arm. Deletion of a 1-kb subregion within the RE, which is not necessary during switching, abolished mating-type-dependent chromosome folding. The RE is therefore a composite element with one subregion essential for donor selection during switching and a separate region involved in modulating chromosome conformation. Yeast mating-type switching involves a mating-type-dependent selection of either the left (HML) or right silent mating-type locus (HMR) on chromosome III for gene conversion with the active MAT locus. One hypothesis has been that this involves differential folding of the chromosome. Belton etal. now show that a 1-kb cis-element located within the larger recombination enhancer determines mating-type-dependent chromosome folding so that in MATa cells HML associates with the centromere and MAT locus more frequently than in MATα cells. © 2015 The Authors. Source

Vlasova A.,Barcelona Institute of Science and Technology BIST | Vlasova A.,University Pompeu Fabra | Capella-Gutierrez S.,Barcelona Institute of Science and Technology BIST | Capella-Gutierrez S.,University Pompeu Fabra | And 53 more authors.
Genome Biology

Background: Legumes are the third largest family of angiosperms and the second most important crop class. Legume genomes have been shaped by extensive large-scale gene duplications, including an approximately 58 million year old whole genome duplication shared by most crop legumes. Results: We report the genome and the transcription atlas of coding and non-coding genes of a Mesoamerican genotype of common bean (Phaseolus vulgaris L., BAT93). Using a comprehensive phylogenomics analysis, we assessed the past and recent evolution of common bean, and traced the diversification of patterns of gene expression following duplication. We find that successive rounds of gene duplications in legumes have shaped tissue and developmental expression, leading to increased levels of specialization in larger gene families. We also find that many long non-coding RNAs are preferentially expressed in germ-line-related tissues (pods and seeds), suggesting that they play a significant role in fruit development. Our results also suggest that most bean-specific gene family expansions, including resistance gene clusters, predate the split of the Mesoamerican and Andean gene pools. Conclusions: The genome and transcriptome data herein generated for a Mesoamerican genotype represent a counterpart to the genomic resources already available for the Andean gene pool. Altogether, this information will allow the genetic dissection of the characters involved in the domestication and adaptation of the crop, and their further implementation in breeding strategies for this important crop. © 2016 Vlasova et al. Source

Chala M.,German Electron Synchrotron | Grojean C.,German Electron Synchrotron | Grojean C.,Catalan Institution for Research and Advanced Studies | Riembau M.,German Electron Synchrotron | And 3 more authors.
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics

The recently observed excess in diphoton events at around 750 GeV can be satisfactorily described in terms of a new spin-0 real singlet with effective interactions to the gauge bosons. In this letter we first review the current constraints on this setup. We further explore the production in association with a gauge boson. We show the potential of this channel to unravel current flat directions in the allowed parameter space. We then study the potential of two different asymmetries for disentangling the CP nature of such a singlet in both gluon fusion and vector-boson fusion. For this matter, we perform an estimation of the efficiency for selecting signal and background events in eight different decay modes, namely 4ℓ,2j2ℓ,2jℓE̸T,2γ2j,4ℓ2j,2ℓγ2j,4j2ℓ and 4jℓE̸T. We emphasize that the very different couplings of this new singlet to the Standard Model particles as well as the larger mass provide a distinctive phenomenology with respect to Higgs searches. We finally show that a large region of the parameter space could be tested within the current LHC run, the dominant channel being 2γ2j. © 2016 The Authors Source

Bogu G.K.,Barcelona Institute of Science and Technology BIST | Bogu G.K.,Barcelona Institute of Science and Technology | Bogu G.K.,University Pompeu Fabra | Vizan P.,Barcelona Institute of Science and Technology | And 11 more authors.
Molecular and Cellular Biology

Discovering and classifying long noncoding RNAs (lncRNAs) across all mammalian tissues and cell lines remains a major challenge. Previously, mouse lncRNAs were identified using transcriptome sequencing (RNA-seq) data from a limited number of tissues or cell lines. Additionally, associating a few hundred lncRNA promoters with chromatin states in a single mouse cell line has identified two classes of chromatin-associated lncRNA. However, the discovery and classification of lncRNAs is still pending in many other tissues in mouse. To address this, we built a comprehensive catalog of lncRNAs by combining known lncRNAs with high-confidence novel lncRNAs identified by mapping and de novo assembling billions of RNA-seq reads from eight tissues and a primary cell line in mouse. Next, we integrated this catalog of lncRNAs with multiple genome-wide chromatin state maps and found two different classes of chromatin state-associated lncRNAs, including promoter-associated (plncRNAs) and enhancer- associated (elncRNAs) lncRNAs, across various tissues. Experimental knockdown of an elncRNA resulted in the downregulation of the neighboring protein-coding Kdm8 gene, encoding a histone demethylase. Our findings provide 2,803 novel lncRNAs and a comprehensive catalog of chromatin-associated lncRNAs across different tissues in mouse. © 2016, American Society for Microbiology. Source

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