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Editorial
. 2020 Feb 4:11:8.
doi: 10.1186/s13100-020-0202-3. eCollection 2020.

Integrating transposable elements in the 3D genome

Alexandros Bousios #  1 , Hans-Wilhelm Nützmann #  2 , Dorothy Buck  3 , Davide Michieletto  3   4   5
Affiliations
Editorial

Integrating transposable elements in the 3D genome

Alexandros Bousios et al. Mob DNA. .

Abstract

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.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
a Coarse graining of microscopic details of double stranded DNA into a bead-spring polymer. b A polymer model for the nucleosome: highlighted are the features of DNA stiffness (set by penalising large angles θ between consecutive pairs of monomers) and connectivity (set by penalising large extensions x between consecutive beads). We also account for excluded volume interactions and pair-attraction represented by the wrapping of the orange segment around the histone octamer (here a blue spherical bead). c Schematics showing that integration events on DNA deform the substrate. d Snapshots from molecular dynamics simulations showing an integration event within a nucleosome. Color scheme: orange = wrapped host DNA, green= viral DNA, grey = non-wrapped host DNA. Adapted from Ref. [54]
Fig. 2
Fig. 2
a Copy-and-paste transposition explores the nuclear space by diffusing from the periphery towards the interior, i.e. outside-in. The large-scale nuclear architecture, i.e. inverted or conventional [95], Lamin Associated Domains (LADs) [21], compartments [71] and enhancers hot-spots [83, 86], are expected to play the biggest roles in the integration site selection. b–c Cut-and-paste transposition explores the nuclear interior inside-out. In this case, TAD-scale (∼1 Mbp) genome folding is expected to dominate and in particular open conformations will yield short range de novo re-integration whereas collapsed ones will lead to longer range re-integration. Duplication of the transposon is also possible by homologous DNA repair of the broken strands
Fig. 3
Fig. 3
a Sketch of the original simulations performed in this work where we consider a segment of DNA 1.6 kbp long (or N=200 beads, each bead representing 8 bp) with rigidity lp=150 bp. The DNA is interspersed with “soft” sites which display a different rigidity lf. The length of these weak sites is 8 bp, or 1 bead. b We compute the frequency of integration events per each segment of the substrate by counting the number of events occurring at a specific locus over the total integration events. We average over 1000 independent simulations. One can notice that the patterns, which are roughly uniform for lf=lp become more and more periodic and reflecting the positions of the soft sites (denoted by the black arrows) when we reduce lf. The dotted line shows the expected frequency for random events 1/N, with N=200 the length of the substrate. For clarity we report only the segment 0.5–1 kbp. c Integration enhancement in soft sites over the expected random frequency. Each box represents a different value of the rigidity of the soft sites lf. Recall that lf=lp=150 bp reflects a uniformly stiff substrate and indeed we recover the expected value (unity) for the enhancement
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References

    1. Deniz Özgen, Frost Jennifer M., Branco Miguel R. Regulation of transposable elements by DNA modifications. Nature Reviews Genetics. 2019;20(7):417–431. doi: 10.1038/s41576-019-0106-6. - DOI - PubMed
    1. Schnable PS, Pasternak S, Liang C, Zhang J, Fulton L, Graves TA, Minx P, Reily AD. Courtney L, Kruchowski SS, Tomlinson C, Strong C, Delehaunty K, Fronick C, Courtney B, Rock SM, Belter E, Du F, Kim K, Abbott RM, Cotton M, Levy A, Marchetto P, Ochoa K, Jackson SM, Gillam B, Chen W, Yan L, Higginbotham J, Cardenas M, Waligorski J, Applebaum E, Phelps L, Falcone J, Kanchi K, Thane T, Scimone A, Thane N, Henke J, Wang T, Ruppert J, Shah N, Rotter K, Hodges J, Ingenthron E, Cordes M, Kohlberg S, Sgro J, Delgado B, Mead K, Chinwalla A, Leonard S, Crouse K, Collura K, Kudrna D, Currie J, He R, Angelova A, Rajasekar S, Mueller T, Lomeli R, Scara G, Ko A, Delaney K, Wissotski M, Lopez G, Campos D, Braidotti M, Ashley E, Golser W, Kim H, Lee S, Lin J, Dujmic Z, Kim W, Talag J, Zuccolo A, Fan C, Sebastian A, Kramer M, Spiegel L, Nascimento L, Zutavern T, Miller B, Ambroise C, Muller S, Spooner W, Narechania A, Ren L, Wei S, Kumari S. The B73 Maize Genome: Complexity, Diversity, and Dynamics. J Sci. 2009;326:1112. - PubMed
    1. Lee HE, Ayarpadikannan S, Kim HS. Role of transposable elements in genomic rearrangement, evolution, gene regulation and epigenetics in primates. Genes Genet Syst. 2016;90(18805779):245. - PubMed
    1. Chuong EB, Elde NC, Feschotte C. Regulatory activities of transposable elements: From conflicts to benefits. Nat Rev Genet. 2017;18(14710064):71. doi: 10.1038/nrg.2016.139. - DOI - PMC - PubMed
    1. Bousios A, Gaut BS. ScienceDirect Mechanistic and evolutionary questions about epigenetic conflicts between transposable elements and their plant hosts. Curr Opin Plant Biol. 2016;30(1369-5266):123. doi: 10.1016/j.pbi.2016.02.009. - DOI - PubMed

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