title: De novo LINE-1 retrotransposition in HepG2 cells preferentially targets gene poor regions of chromosome 13.
abstract: Long interspersed nuclear elements (Line-1 or L1s) account for ~17% of the human genome. While the majority of human L1s are inactive, ~80-100 elements remain retrotransposition competent and mobilize through RNA intermediates to different locations within the genome. De novo insertions of L1s account for polymorphic variation of the human genome and disruption of target loci at their new location. In the present study, fluorescence in situ hybridization and DNA sequencing were used to characterize retrotransposition profiles of L1(RP) in cultured human HepG2 cells. While expression of synthetic L1(RP) was associated with full-length and truncated insertions throughout the entire genome, a strong preference for gene-poor regions, such as those found in chromosome 13 was observed for full-length insertions. These findings shed light into L1 targeting mechanisms within the human genome and question the putative randomness of L1 retrotransposition.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA.
authors.forename: Pasano
authors.initials: P
authors.lastname: Bojang
authors.affiliation: Department of Toxicology Sciences, Safety Assessment, AstraZeneca R&D, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Anderton
authors.affiliation: Department of Toxicology Sciences, Safety Assessment, AstraZeneca R&D, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Roberts
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA; Center for Environmental Genomics and Integrative Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA. Electronic address: ksramos@email.arizona.edu.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Ramos
mesh_terms: D001483:Base Sequence; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D003001:Cloning, Molecular; D015894:Genome, Human; D056945:Hep G2 Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010957:Plasmids / Q000235:genetics; D017422:Sequence Analysis, DNA
keywords: Chromosome 13; Fluorescence in situ hybridization; HepG2; Long interspersed nuclear element-1 (Line-1/L1); Retrotransposons