Year: 2013
Type: article
Abstract: LINE-1 (L1) retrotransposons make up a significant portion of human genomes, with an estimated 500,000 copies per genome.Like other retrotransposons, L1 retrotransposons propagate through RNA sequences that are reverse transcribed into DNA sequences, which are integrated into new genomic loci.L1 somatic insertions have the potential to disrupt the transcriptome by inserting into or nearby genes.By mutating genes and playing a role in epigenetic dysregulation, L1 transposons may contribute to tumorigenesis.Studies of the ''mobilome'' have lagged behind other tumor characterizations at the sequence, transcript, and epigenetic levels.Here, we consider evidence that L1 retrotransposons may sometimes drive human tumorigenesis. Inhibition of L1 Retrotransposition in Normal Germline and Somatic CellsL1 is regulated by distinct pathways in different cell contexts.In the male germline, L1 is inhibited via an elaborate system involving Piwi-interacting RNAs (piRNAs) that ultimately methylates genomic L1 sequences.This depends on methylation regulator DNMT3L [6] and PIWIL4 (also known as MIWI2) [7], as well as PIWI proteins involved in piRNA production.In embryonic stem cells, which can be used to model chromatin regulation in preimplantation-stage embryos, inherited L1 methylation is maintained by DNA methyltransferases DNMT1, DNMT3A, and DNMT3B [8].In embryonal carcinoma cell lines, which are sometimes used for the same purpose, newly
Source: PLoS Genetics
Authors: Nemanja Rodić, Kathleen H. Burns
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
OpenAlex ID: W2070164706