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 [FR] Region Centre-Val de Loire [FR] Ligue Nationale Contre le Cancer [FR] NCI - National Cancer Institute [US-MD] [US-MD]
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.
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