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The last 50 bibliographies

Loss of SET1/COMPASS methyltransferase activity reduces lifespan and fertility in Caenorhabditis elegans.

Author(s) : Caron M, Gely L, Garvis S, Adrait A, Couté Y, Palladino F, Fabrizio P,
Journal : Life Sci Alliance
2022
Changes in histone post-translational modifications are associated with agingthrough poorly defined mechanisms. Histone 3 lysine 4 (H3K4) methylation atpromoters is deposited by SET1 family methyltransferases acting within conservedmultiprotein complexes known as COMPASS. Previous work yielded conflicting resultsabout the requirement for H3K4 methylation during aging. Here, we reassessed therole of SET1/COMPASS-dependent H3K4 methylation in Caenorhabditis elegans lifespanand fertility by generating set-2(syb2085) mutant animals that express acatalytically inactive form of SET-2, the C. elegans SET1 homolog. We show thatset-2(syb2085) animals retain the ability to form COMPASS, but have a marked globalloss of H3K4 di- and trimethylation (H3K4me2/3). Reduced H3K4 methylation wasaccompanied by loss of fertility, as expected; however, in contrast to earlierstudies, set-2(syb2085) mutants displayed a significantly shortened, not extended,lifespan and had normal intestinal fat stores. Other commonly used set-2 mutantswere also short-lived, as was a cfp-1 mutant that lacks the SET1/COMPASSchromatin-targeting component. These results challenge previously held views andestablish that WT H3K4me2/3 levels are essential for normal lifespan in C. elegans.

Ribosome dynamics and mRNA turnover, a complex relationship under constant cellular scrutiny.

Author(s) : Morris C, Cluet D, Ricci E,
Journal : Wiley Interdiscip Rev RNA
2021
Eukaryotic gene expression is closely regulated by translation and turnover ofmRNAs. Recent advances highlight the importance of translation in the control ofmRNA degradation, both for aberrant and apparently normal mRNAs. During translation,the information contained in mRNAs is decoded by ribosomes, one codon at a time, andtRNAs, by specifically recognizing codons, translate the nucleotide code into aminoacids. Such a decoding step does not process regularly, with various obstacles thatcan hinder ribosome progression, then leading to ribosome stalling or collisions.The progression of ribosomes is constantly monitored by the cell which has evolvedseveral translation-dependent mRNA surveillance pathways, includingnonsense-mediated decay (NMD), no-go decay (NGD), and non-stop decay (NSD), todegrade certain problematic mRNAs and the incomplete protein products. Recentprogress in sequencing and ribosome profiling has made it possible to discover newmechanisms controlling ribosome dynamics, with numerous crosstalks betweentranslation and mRNA decay. We discuss here various translation features criticalfor mRNA decay, with particular focus on current insights from the complexity of thegenetic code and also the emerging role for the ribosome as a regulatory huborchestrating mRNA decay, quality control, and stress signaling. Even if theinterplay between mRNA translation and degradation is no longer to be demonstrated,a better understanding of their precise coordination is worthy of furtherinvestigation. This article is categorized under: RNA Turnover and Surveillance >Regulation of RNA Stability Translation > Translation Regulation RNA Interactionswith Proteins and Other Molecules > RNA-Protein Complexes.

Best practices for the visualization, mapping, and manipulation of R-loops.

Author(s) : Chédin F, Hartono S, Sanz L, Vanoosthuyse V,
Journal : EMBO J
2021
R-loops represent an abundant class of large non-B DNA structures in genomes. Eventhough they form transiently and at modest frequencies, interfering with R-loopformation or dissolution has significant impacts on genome stability. Addressing themechanism(s) of R-loop-mediated genome destabilization requires a precisecharacterization of their distribution in genomes. A number of independent methodshave been developed to visualize and map R-loops, but their results are at timesdiscordant, leading to confusion. Here, we review the main existing methodologiesfor R-loop mapping and assess their limitations as well as the robustness ofexisting datasets. We offer a set of best practices to improve the reproducibilityof maps, hoping that such guidelines could be useful for authors and referees alike.Finally, we propose a possible resolution for the apparent contradictions in R-loopmapping outcomes between antibody-based and RNase H1-based mapping approaches.

RNA polymerase backtracking results in the accumulation of fission yeast condensin at active genes.

Author(s) : Rivosecchi J, Jost D, Vachez L, Gautier F, Bernard P, Vanoosthuyse V,
Journal : Life Sci Alliance
2021
The mechanisms leading to the accumulation of the SMC complexes condensins aroundspecific transcription units remain unclear. Observations made in bacteria suggestedthat RNA polymerases (RNAPs) constitute an obstacle to SMC translocation,particularly when RNAP and SMC travel in opposite directions. Here we show infission yeast that gene termini harbour intrinsic condensin-accumulating featureswhatever the orientation of transcription, which we attribute to the frequentbacktracking of RNAP at gene ends. Consistent with this, to relocate backtrackedRNAP2 from gene termini to gene bodies was sufficient to cancel the accumulation ofcondensin at gene ends and to redistribute it evenly within transcription units,indicating that RNAP backtracking may play a key role in positioning condensin.Formalization of this hypothesis in a mathematical model suggests that the inclusionof a sub-population of RNAP with longer dwell-times is essential to fullyrecapitulate the distribution profiles of condensin around active genes. Takentogether, our data strengthen the idea that dense arrays of proteins tightly boundto DNA alter the distribution of condensin on chromosomes.

Mutational sources of trans-regulatory variation affecting gene expression in Saccharomyces cerevisiae.

Author(s) : Duveau F, Vande Zande P, Metzger B, Diaz C, Walker E, Tryban S, Siddiq M, Yang B, Wittkopp P,
Journal : Elife
2021
Heritable variation in a gene's expression arises from mutations impacting cis- andtrans-acting components of its regulatory network. Here, we investigate howtrans-regulatory mutations are distributed within the genome and within a generegulatory network by identifying and characterizing 69 mutations withtrans-regulatory effects on expression of the same focal gene in Saccharomycescerevisiae. Relative to 1766 mutations without effects on expression of this focalgene, we found that these trans-regulatory mutations were enriched in codingsequences of transcription factors previously predicted to regulate expression ofthe focal gene. However, over 90% of the trans-regulatory mutations identifiedmapped to other types of genes involved in diverse biological processes includingchromatin state, metabolism, and signal transduction. These data show how geneticchanges in diverse types of genes can impact a gene's expression in trans, revealingproperties of trans-regulatory mutations that provide the raw material fortrans-regulatory variation segregating within natural populations.

Polymer modelling unveils the roles of heterochromatin and nucleolar organizing regions in shaping 3D genome organization in Arabidopsis thaliana.

Author(s) : Di Stefano M, Nützmann H, Marti-Renom M, Jost D,
Journal : Nucleic Acids Res
2021
The 3D genome is characterized by a complex organization made of genomic andepigenomic layers with profound implications on gene regulation and cell function.However, the understanding of the fundamental mechanisms driving the crosstalkbetween nuclear architecture and (epi)genomic information is still lacking. Theplant Arabidopsis thaliana is a powerful model organism to address these questionsowing to its compact genome for which we have a rich collection of microscopy,chromosome conformation capture (Hi-C) and ChIP-seq experiments. Using polymermodelling, we investigate the roles of nucleolus formation and epigenomics-driveninteractions in shaping the 3D genome of A. thaliana. By validation of severalpredictions with published data, we demonstrate that self-attracting nucleolarorganizing regions and repulsive constitutive heterochromatin are major mechanismsto regulate the organization of chromosomes. Simulations also suggest thatinterphase chromosomes maintain a partial structural memory of the V-shapes, typicalof (sub)metacentric chromosomes in anaphase. Additionally, self-attraction betweenfacultative heterochromatin regions facilitates the formation of Polycomb bodieshosting H3K27me3-enriched gene-clusters. Since nucleolus and heterochromatin arehighly-conserved in eukaryotic cells, our findings pave the way for a comprehensivecharacterization of the generic principles that are likely to shape and regulate the3D genome in many species.

4D nucleome modeling.

Author(s) : Di Stefano M, Paulsen J, Jost D, Marti-Renom M,
Journal : Curr Opin Genet Dev
2021
The intrinsic dynamic nature of chromosomes is emerging as a fundamental componentin regulating DNA transcription, replication, and damage-repair among other nuclearfunctions. With this increased awareness, reinforced over the last ten years, manynew experimental techniques, mainly based on microscopy and chromosome conformationcapture, have been introduced to study the genome in space and time. Owing to theincreasing complexity of these cutting-edge techniques, computational approacheshave become of paramount importance to interpret, contextualize, and complement suchexperiments with new insights. Hence, it is becoming crucial for experimentalbiologists to have a clear understanding of the diverse theoretical modelingapproaches available and the biological information each of them can provide.

Comparison of lipidome profiles of Caenorhabditis elegans-results from an inter-laboratory ring trial.

Author(s) : Spanier B, Laurençon A, Weiser A, Pujol N, Omi S, Barsch A, Korf A, Meyer S, Ewbank J, Paladino F, Garvis S, Aguilaniu H, Witting M,
Journal : Metabolomics
2021
INTRODUCTION: Lipidomic profiling allows 100s if not 1000s of lipids in a sample tobe detected and quantified. Modern lipidomics techniques are ultra-sensitive assaysthat enable the discovery of novel biomarkers in a variety of fields and provide newinsight in mechanistic investigations. Despite much progress in lipidomics, thereremains, as for all high throughput "omics" strategies, the need to developstrategies to standardize and integrate quality control into studies in order toenhance robustness, reproducibility, and usability of studies within specific fieldsand beyond. OBJECTIVES: We aimed to understand how much results from lipid profilingin the model organism Caenorhabditis elegans are influenced by different cultureconditions in different laboratories. METHODS: In this work we have undertaken aninter-laboratory study, comparing the lipid profiles of N2 wild type C. elegans anddaf-2(e1370) mutants lacking a functional insulin receptor. Sample were collectedfrom worms grown in four separate laboratories under standardized growth conditions.We used an UPLC-UHR-ToF-MS system allowing chromatographic separation before MSanalysis. RESULTS: We found common qualitative changes in several marker lipids insamples from the individual laboratories. On the other hand, even in this controlledexperimental system, the exact fold-changes for each marker varied betweenlaboratories. CONCLUSION: Our results thus reveal a serious limitation to thereproducibility of current lipid profiling experiments and reveal challenges to theintegration of such data from different laboratories.

A single-chain and fast-responding light-inducible Cre recombinase as a novel optogenetic switch.

Author(s) : Duplus-Bottin H, Spichty M, Triqueneaux G, Place C, Mangeot P, Ohlmann T, Vittoz F, Yvert G,
Journal : Elife
2021
Optogenetics enables genome manipulations with high spatiotemporal resolution,opening exciting possibilities for fundamental and applied biological research.Here, we report the development of LiCre, a novel light-inducible Cre recombinase.LiCre is made of a single flavin-containing protein comprising the AsLOV2photoreceptor domain of Avena sativa fused to a Cre variant carrying destabilizingmutations in its N-terminal and C-terminal domains. LiCre can be activated withinminutes of illumination with blue light, without the need of additional chemicals.When compared to existing photoactivatable Cre recombinases based on two splitunits, LiCre displayed faster and stronger activation by light as well as a lowerresidual activity in the dark. LiCre was efficient both in yeast, where it allowedus to control the production of β-carotene with light, and in human cells. Given itssimplicity and performances, LiCre is particularly suited for fundamental andbiomedical research, as well as for controlling industrial bioprocesses.