De novo LINE-1 retrotransposition in HepG2 cells preferentially targets gene poor regions of chromosome 13

• L1 retrotransposition in HepG2 cells is not an entirely random process.
• L1 exhibits a preference for insertion into gene-poor regions such as those found in chromosome 13.
• FISH provides a tool to identify full-length and truncated L1 insertions into the host genome.
• Identifying L1 insertions at the chromosome level may define the genomic basis of human disease.

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 L1RP in cultured human HepG2 cells. While expression of synthetic L1RP 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.