DNA cleavage; insertion preference; neuron; transposon; vertebrate; DNA Transposable Elements; Nerve Tissue Proteins; PGBD1 protein, human; PGBD5 protein, human; Transposases; Animals; Chromosomes/genetics; DNA Transposable Elements/genetics; HeLa Cells; Humans; Mice; Nerve Tissue Proteins/genetics; Protein Domains/genetics; Recombination, Genetic; Transposases/genetics; Chromosomes; Protein Domains; Biophysics; Structural Biology; Molecular Biology
Abstract :
[en] PiggyBac(PB)-like elements (pble) are members of a eukaryotic DNA transposon family. This family is of interest to evolutionary genomics because pble transposases have been domesticated at least 9 times in vertebrates. The amino acid sequence of pble transposases can be split into three regions: an acidic N-terminal domain (~100 aa), a central domain (~400 aa) containing a DD[D/E] catalytic triad, and a cysteine-rich domain (CRD; ~90 aa). Two recent reports suggested that a functional CRD is required for pble transposase activity. Here we found that two CRD-deficient pble transposases, a PB variant and an isoform encoded by the domesticated PB-derived vertebrate transposase gene 5 (pgbd5) trigger transposition of the Ifp2 pble. When overexpressed in HeLa cells, these CRD-deficient transposases can insert Ifp2 elements with proper and improper transposon ends, associated with deleterious effects on cells. Finally, we found that mouse CRD-deficient transposase Pgbd5, as well as PB, do not insert pbles at random into chromosomes. Transposition events occurred more often in genic regions, in the neighbourhood of the transcription start sites and were often found in genes predominantly expressed in the human central nervous system.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Helou, Laura ; Université de Liège - ULiège > Département des sciences cliniques ; PRC, UMR INRAE 0085, CNRS 7247, Centre INRAE Val de Loire, 37380 Nouzilly, France
Beauclair, Linda; PRC, UMR INRAE 0085, CNRS 7247, Centre INRAE Val de Loire, 37380 Nouzilly, France
Dardente, Hugues; PRC, UMR INRAE 0085, CNRS 7247, Centre INRAE Val de Loire, 37380 Nouzilly, France
Arensburger, Peter; Biological Sciences Department, California State Polytechnic University, Pomona, CA 91768, USA
Buisine, Nicolas; UMR CNRS 7221, Muséum National d'Histoire Naturelle, 75005 Paris, France
Jaszczyszyn, Yan; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France
Guillou, Florian; PRC, UMR INRAE 0085, CNRS 7247, Centre INRAE Val de Loire, 37380 Nouzilly, France
Lecomte, Thierry; EA GICC 7501, CHRU de Tours, 37044 Tours Cedex 09, France
Kentsis, Alex; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, Cornell University, New York, NY, USA, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Bigot, Yves; PRC, UMR INRAE 0085, CNRS 7247, Centre INRAE Val de Loire, 37380 Nouzilly, France. Electronic address: yves.bigot@inrae.fr
Language :
English
Title :
The C-terminal Domain of piggyBac Transposase Is Not Required for DNA Transposition.
SNFGE - Société Nationale Française de Gastro-Entérologie Region Centre-Val de Loire Ligue Nationale Contre le Cancer NCI - National Cancer Institute
Funding text :
This work was supported by the C.N.R.S. the I.N.R.A. and the GDR CNRS 2157. It also received funds from a research program grants from the Ligue Nationale Contre le Cancer, the Merck foundation, and the French National Society of Gastroenterology. Laura Helou holds a PhD fellowship from the Région Centre Val de Loire. We acknowledge the high-throughput sequencing facility of I2BC for its sequencing and bioinformatics expertise. Alex Kentsis is a consultant for Novartis and is supported by the National Cancer Institute grants R01 CA214812 and P30 CA008748. Yves Bigot, who was in charge of the achievement of this project does not have to thank the French National Research Agency for its financial support but he kindly thanks it for the excellent reviews embellished with arguments based on scientific and cultural novelties in the expertise of his yearly application file during the last decade.This work was supported by the C.N.R.S., the I.N.R.A., and the GDR CNRS 2157. It also received funds from a research program grants from the Ligue Nationale Contre le Cancer, the Merck foundation, and the French National Society of Gastroenterology. Laura Helou holds a PhD fellowship from the Région Centre Val de Loire. We acknowledge the high-throughput sequencing facility of I2BC for its sequencing and bioinformatics expertise. Alex Kentsis is a consultant for Novartis and is supported by the National Cancer Institute grants R01 CA214812 and P30 CA008748. Yves Bigot, who was in charge of the achievement of this project does not have to thank the French National Research Agency for its financial support but he kindly thanks it for the excellent reviews embellished with arguments based on scientific and cultural novelties in the expertise of his yearly application file during the last decade.
Piégu, B., Bire, S., Arensburger, P., Bigot, Y., A survey of transposable element classification systems–a call for a fundamental update to meet the challenge of their diversity and complexity. Mol. Phylogenet. Evol. 86 (2016), 90–109.
Arensburger, P., Piégu, B., Bigot, Y., The future of transposable element annotation and their classification in the light of functional genomics - what we can learn from the fables of Jean de la Fontaine?. Mob. Genet. Elements, 6, 2016, e1256852.
Arkhipova, I.R., Using bioinformatic and phylogenetic approaches to classify transposable elements and understand their complex evolutionary histories. Mob. DNA, 8, 2017, 19.
Bouallègue, M., Rouault, J.D., Hua-Van, A., Makni, M., Capy, P., Molecular evolution of piggyBac superfamily: From selfishness to domestication. Gen. Biol. Evol. 9 (2017), 323–339.
Cary, L.C., Goebel, M., Corsaro, B.G., Wang, H.G., Rosen, E., Fraser, M.J., Transposon mutagenesis of baculoviruses: analysis of Trichoplusia ni transposon IFP2 insertions within the FP-locus of nuclear polyhedrosis viruses. Virology 172 (1989), 156–169.
Yusa, K., piggyBac transposon. Microbiol. Spectr., 3, 2015 MDNA3-0028-2014.
Chen, Q., Luo, W., Veach, R.A., Hickman, A.B., Wilson, M.H., Dyda, F., Structural basis of seamless excision and specific targeting by piggyBac transposase. Nat. Commun., 11, 2020, 3446.
Morellet, N., Li, X., Wieninger, S.A., Taylor, J.L., Bischerour, J., Moriau, S., Lescop, E., Bardiaux, B., Mathy, N., et al. Sequence-specific DNA binding activity of the cross-brace zinc finger motif of the piggyBac transposase. Nucl. Acids Res. 46 (2018), 2660–2677.
Sharma, R., Nirwal, S., Narayanan, N., Nair, D.T., Dimerization through the RING-Finger domain attenuates excision activity of the piggyBac transposase. Biochemistry 57 (2018), 2913–2922.
Keith, J.H., Fraser, T.S., Fraser, M.J. Jr., Analysis of the piggyBac transposase reveals a functional nuclear targeting signal in the 94 c-terminal residues. BMC Mol. Biol., 9, 2008, 72.
Hong, J.B., Chou, F.J., Ku, A.T., Fan, H.H., Lee, T.L., Huang, Y.H., Yang, T.L., Su, I.C., et al. A nucleolus-predominant piggyBac transposase, NP-mPB, mediates elevated transposition efficiency in mammalian Cells. PLoS One, 9, 2014, e89396.
Luo, W., Galvan, D.L., Woodard, L.E., Dorset, D., Levy, S., Wilson, M.H., Comparative analysis of chimeric ZFP-, TALE- and Cas9-piggyBac transposases for integration into a single locus in human cells. Nucl. Acids Res. 45 (2017), 8411–8422.
Henssen, A.G., Koche, R., Zhuang, J., Jiang, E., Reed, C., Eisenberg, A., Still, E., MacArthur, I.C., et al. PGBD5 promotes site-specific oncogenic mutations in human tumors. Nat. Genet. 49 (2017), 1005–1014.
Wang, H., Mayhew, D., Chen, X., Johnston, M., Mitra, R.D., “Calling cards” for DNA-binding proteins in mammalian cells. Genetics 190 (2012), 941–949.
Li, M.A., Pettitt, S.J., Eckert, S., Ning, Z., Rice, S., Cadiñanos, J., Yusa, K., Conte, N., Bradley, A., The piggyBac transposon displays local and distant reintegration preferences and can cause mutations at noncanonical integration sites. Mol. Cell. Biol. 33 (2013), 1317–1330.
Elick, T.A., Lobo, N., Fraser, M.J. Jr., Analysis of the cis-acting DNA elements required for piggyBac transposable element excision. Mol. Gen. Genet. 255 (1997), 605–610.
Mitra, R., Fain-Thornton, J., Craig, N.L., piggyBac can bypass DNA synthesis during cut and paste transposition. EMBO J. 27 (2008), 1097–1109.
Pavelitz, T., Gray, L.T., Padilla, S.L., Bailey, A.D., Weiner, A.M., PGBD5: a neural-specific intron containing piggyBac transposase domesticated over 500 million years ago and conserved from cephalochordates to humans. Mob. DNA 4 (2013), 23–39.
Henssen, A.G., Henaff, E., Jiang, E., Eisenberg, A.R., Carson, J.R., Villasante, C.M., Ray, M., Still, E., et al. Genomic DNA transposition induced by human PGBD5. Elife, 4, 2015, e10565.
Lohe, A.R., Timmons, C., Beerman, I., Lozovskaya, E.R., Hartl, D.L., Self-inflicted wounds, template-directed gap repair and a recombination hotspot. Effects of the mariner transposase. Genetics 154 (2000), 647–656.
Woodard, L.E., Li, X., Malani, N., Kaja, A., Hice, R.H., Atkinson, P.W., Bushman, F.D., Craig, N.L., Wilson, M.H., Comparative analysis of the recently discovered hAT transposon TcBuster in human cells. PLoS One, 7, 2012, e42666.
Wilson, M.H., Coates, C.J., George, A.L. Jr., PiggyBac transposon-mediated gene transfer in human cells. Mol. Ther. 15 (2007), 139–145.
Huang, X., Guo, H., Tammana, S., Jung, Y.C., Mellgren, E., Bassi, P., Cao, Q., Tu, Z.J., et al. Gene transfer efficiency and genome-wide integration profiling of Sleeping Beauty, Tol2, and piggyBac transposons in human primary T cells. Mol. Ther. 18 (2010), 1803–1813.
Gogol-Döring, A., Ammar, I., Gupta, S., Bunse, M., Miskey, C., Chen, W., Uckert, W., Schulz, T.F., et al. Genome-wide profiling reveals remarkable parallels between insertion site selection properties of the MLV retrovirus and the piggyBac transposon in primary human CD4(+) T cells. Mol. Ther. 24 (2016), 592–606.
Landry, J.J., Pyl, P.T., Rausch, T., Zichner, T., Tekkedil, M.M., Stütz, A.M., Jauch, A., Aiyar, R.S., et al. The genomic and transcriptomic landscape of a HeLa cell line. G3 (Bethesda) 3 (2013), 1213–1224.
Adey, A., Burton, J.N., Kitzman, J.O., Hiatt, J.B., Lewis, A.P., Martin, B.K., Qiu, R., Lee, C., Shendure, J., The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line. Nature 500 (2013), 207–211.
Lin, Y.C., Boone, M., Meuris, L., Lemmens, I., Van Roy, N., Soete, A., Reumers, J., Moisse, M., et al. Genome dynamics of the human embryonic kidney 293 lineage in response to cell biology manipulations. Nat. Commun., 5, 2014, 4767.
Liu, Y., Mi, Y., Mueller, T., Kreibich, S., Williams, E.G., Van Drogen, A., Borel, C., Frank, M., et al. Multi-omic measurements of heterogeneity in HeLa cells across laboratories. Nat. Biotechnol. 37 (2019), 314–322.
Negi, S.K., Guda, C., Global gene expression profiling of healthy human brain and its application in studying neurological disorders. Sci. Rep., 7, 2017, 897.
Zhang, Y., Cheng, T.C., Huang, G., Lu, Q., Surleac, M.D., Mandell, J.D., Pontarotti, P., Petrescu, A.J., et al. Transposon molecular domestication and the evolution of the RAG recombinase. Nature 569 (2019), 79–84.
Guizard, S., Piégu, B., Arensburger, P., Guillou, F., Bigot, Y., Deep landscape update of dispersed and tandem repeats in the genome model of the red jungle fowl, Gallus gallus, using a series of de novo investigating tools. BMC Genom., 17, 2016, 659.
Kapusta, A., Suh, A., Evolution of bird genomes-a transposon's-eye view. Ann. N. Y. Acad. Sci. 1389 (2017), 164–185.
Bire, S., Ley, D., Casteret, S., Mermod, N., Bigot, Y., Rouleux-Bonnin, F., Optimization of the piggyBac transposon using mRNA and insulators: toward a more reliable gene delivery system. PLoS One, 8, 2013, e82559.
Travnickova-Bendova, Z., Cermakian, N., Reppert, S.M., Sassone-Corsi, P., Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity. Proc. Natl. Acad. Sci. USA 99 (2002), 7728–7733.
Bire, S., Casteret, S., Piégu, B., Beauclair, L., Moiré, N., Arensbuger, P., Bigot, Y., Mariner transposons contain a silencer: Possible role of the polycomb repressive complex 2. PLoS Genet., 12, 2016, e1005902.
Demattei, M.V., Hedhili, S., Sinzelle, L., Bressac, C., Casteret, S., Moiré, N., Cambefort, J., Thomas, X., et al. Nuclear importation of Mariner transposases among eukaryotes: motif requirements and homo-protein interactions. PLoS One, 6, 2011, e23693.
Bartholomae, C.C., Glimm, H., von Kalle, C., Schmidt, M., Insertion site pattern: global approach by linear amplification-mediated PCR and mass sequencing. Meth. Mol. Biol. 859 (2012), 255–265.
Bolger, A.M., Lohse, M., Usadel, B., Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30 (2014), 2114–2120.
Li, H., Durbin, R., Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26 (2010), 589–595.
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., et al. The sequence alignment/map (SAM) format and SAMtools. Bioinformatics 25 (2009), 2078–2079.
Quinlan, A.R., Hall, I.M., BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26 (2010), 841–842.
Layer, R.M., Chiang, C., Quinlan, A.R., Hall, I.M., LUMPY: a probabilistic framework for structural variant discovery. Gen. Biol., 15, 2014, R84.
Bindea, G., Mlecnik, B., Hackl, H., Charoentong, P., Tosolini, M., Kirilovsky, A., Fridman, W.F., Pagès, F., et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25 (2009), 1091–1093.
Mlecnik, B., Galon, J., Bindea, G., Comprehensive functional analysis of large lists of genes and proteins. J. Proteom. 171 (2018), 2–10.
Ambrosini, G., Groux, R., Bucher, P., PWMScan: A fast tool for scanning entire genomes with a position-specific weight matrix. Bioinformatics 34 (2018), 2483–2484.
