Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Tye7 regulates yeast Ty1 retrotransposon sense and antisense transcription in response to adenylic nucleotides stress

Transposable elements play a fundamental role in genome evolution. It is proposed that their mobility, activated under stress, induces mutations that could confer advantages to the host organism. Transcription of the Ty1 LTR-retrotransposon of Saccharomyces cerevisiae is activated in response to a severe deficiency in adenylic nucleotides. Here, we show that Ty2 and Ty3 are also stimulated under these stress conditions, revealing the simultaneous activation of three active Ty retrotransposon families. We demonstrate that Ty1 activation in response to adenylic nucleotide depletion requires the DNA-binding transcription factor Tye7. Ty1 is transcribed in both sense and antisense directions. We identify three Tye7 potential binding sites in the region of Ty1 DNA sequence where antisense transcription starts. We show that Tye7 binds to Ty1 DNA and regulates Ty1 antisense transcription. Altogether, our data suggest that, in response to adenylic nucleotide reduction, TYE7 is induced and activates Ty1 mRNA transcription, possibly by controlling Ty1 antisense transcription. We also provide the first evidence that Ty1 antisense transcription can be regulated by environmental stress conditions, pointing to a new level of control of Ty1 activity by stress, as Ty1 antisense RNAs play an important role in regulating Ty1 mobility at both the transcriptional and post-transcriptional stages

Genome-Wide Distribution of RNA-DNA Hybrids Identifies RNase H Targets in tRNA Genes, Retrotransposons and Mitochondria

During transcription, the nascent RNA can invade the DNA template, forming extended RNA-DNA duplexes (R-loops). Here we employ ChIP-seq in strains expressing or lacking RNase H to map targets of RNase H activity throughout the budding yeast genome. In wild-type strains, R-loops were readily detected over the 35S rDNA region, transcribed by Pol I, and over the 5S rDNA, transcribed by Pol III. In strains lacking RNase H activity, R-loops were elevated over other Pol III genes, notably tRNAs, SCR1 and U6 snRNA, and were also associated with the cDNAs of endogenous TY1 retrotransposons, which showed increased rates of mobility to the 5'-flanking regions of tRNA genes. Unexpectedly, R-loops were also associated with mitochondrial genes in the absence of RNase H1, but not of RNase H2. Finally, R-loops were detected on actively transcribed protein-coding genes in the wild-type, particularly over the second exon of spliced ribosomal protein genes

Two large-scale analyses of Ty1 LTR-retrotransposon <it>de novo</it> insertion events indicate that Ty1 targets nucleosomal DNA near the H2A/H2B interface

<p>Abstract</p> <p>Background</p> <p>Over the years, a number of reports have revealed that Ty1 integration occurs in a 1-kb window upstream of Pol III-transcribed genes with an approximate 80-bp periodicity between each integration hotspot and that this targeting requires active Pol III transcription at the site of integration. However, the molecular bases of Ty1 targeting are still not understood.</p> <p>Findings</p> <p>The publications by Baller et al. and Mularoni et al. in the April issue of Genome Res. report the first high-throughput sequencing analysis of Ty1 de novo insertion events. Their observations converge to the same conclusion, that Ty1 targets a specific surface of the nucleosome at he H2A/H2B interface.</p> <p>Conclusion</p> <p>This discovery is important, and should help identifying factor(s) involved in Ty1 targeting. Recent data on transposable elements and retroviruses integration site choice obtained by large-scale analyses indicate that transcription and chromatin structure play an important role in this process. The studies reported in this commentary add a new evidence of the importance of chromatin in integration selectivity that should be of interest for everyone interested in transposable elements integration.</p

Data from: Evolution of a dominant natural isolate of Escherichia coli in the human gut over the course of a year suggests a neutral evolution with reduced effective population size

In vitro and in vivo evolution experiments on Escherichia coli revealed several principles of bacterial adaptation. However, few data are available in the literature describing the behavior of E. coli in its natural environment. We attempted here to study the evolution in the human gut of a commensal dominant E. coli clone ED1a belonging to B2 phylogroup, through a longitudinal genomic study. We sequenced 24 isolates sampled at three different time points within a healthy individual over almost a year. We computed amutation rate of 6.90x10-7 per base per year of the chromosome for E. coli ED1a in healthy human gut. We observed a very limited genomic diversity, and could not detect any evidence of selection contrary to what is observed in experimental evolution over similar length of time. We therefore suggest that ED1a being well adapted to the healthy human gut evolves mostly neutrally with a low effective population size (Ne ≈ 500 – 1700)

Characterization and rapid identification of phylogroup G in Escherichia coli, a lineage with high virulence and antibiotic resistance potential

The phylogeny of the Escherichia coli species, with the identification of seven phylogroups (A, B1, B2, C, D, E and F), is linked to the lifestyle of the strains. With the accumulation of whole genome sequence data, it became clear that some strains belong to a group intermediate between the F and B2 phylogroups, designated as phylogroup G. Here, we studied the complete sequences of 112 strains representative of the G phylogroup diversity and showed that it is composed of one main sequence type complex (STc)117 and four other STcs (STc657, STc454, STc738 and STc174). STc117, which phylogeny is characterized by very short internal branches, exhibits extensive O diversity, but little H-type and fimH allele diversity, whereas the other STcs are characterized by a main O, H and fimH type. STc117 strains possess many traits associated with extra-intestinal virulence, are virulent in a mouse sepsis model and exhibit multi-drug resistance such as CTX-M production. Epidemiologic data on 4,524 Australian and French strains suggest that STc117 is a poultry-associated lineage that can also establish in humans and cause extra-intestinal diseases. We propose an easy identification method that will help to trace this potentially virulent and resistant phylogroup in epidemiologic studies.This work was partially supported by the “Fondation pour la Recherche Médicale” (Equipe FRM 2016, grant number DEQ20161136698)

The growing chaos of tuberculosis population genomics at the era of 'Big Data’: sorting out the wheat from the chaff

International audience<div&gtThe publication of a couple of recent landmark papers (Freschi et al. 2021, Napier et al. 2021, Coscolla et al. 2021, Thawornwattana et al. 2021) claiming the discovery of new WGS-defined clades, prompted us to reevaluate both the SNP informativity and the hierarchical naming of some of the phylogenetical structures described in these articles. Thanks to a new proprietary informatical platform, TB-ANNOTATOR, we performed a benchmark analysis of these articles, and present results that allow to create new links between the pre-genomic and the post-genomic era for young researchers entering into the field, reassessing the SNP informativity, the link between polymorhic markers, and showing current discrepancies between studies, suggesting that even in large databases, the global population structure of &nbsp;MTBC remains strongly dependent on sample origin, WGS quality and bioinformatical tools. We also describe some recent improvements in phylogenetical analysis of MTBC.</div&gt<div&gt<br&gt</div&g

International Congress on Transposable elements (ICTE 2016) in Saint Malo: mobile elements under the sun of Brittany

Abstract The third international conference on Transposable Elements (ICTE) was held 16–19 April 2016 in Saint Malo, France. Organized by the French Transposition Community (Research group of the CNRS: “Mobile genetic elements: from mechanism to populations, an integrative approach”) and the French Society of Genetics, the conference’s goal was to bring together researchers who study transposition in diverse organisms, using multiple experimental approaches. The meeting gathered 180 participants from all around the world. Most of them contributed through poster presentations, invited talks and short talks selected from poster abstracts. The talks were organized into six scientific sessions: “Taming mobile DNA: self and non-self recognition”; “Trans-generational inheritance”; “Mobile DNA genome structure and organization, from molecular mechanisms to applications”; “Remembrance of (retro)transposon past: mobile DNA in genome evolution”; and finally “The yin and the yang of mobile DNA in human health”