Ewing, Adam DSmits, NathanSanchez-Luque, Francisco JFaivre, JamilaBrennan, Paul MRichardson, Sandra RCheetham, Seth WFaulkner, Geoffrey J2023-02-092023-02-092020-11-12http://hdl.handle.net/10668/16598Transposable elements (TEs) drive genome evolution and are a notable source of pathogenesis, including cancer. While CpG methylation regulates TE activity, the locus-specific methylation landscape of mobile human TEs has to date proven largely inaccessible. Here, we apply new computational tools and long-read nanopore sequencing to directly infer CpG methylation of novel and extant TE insertions in hippocampus, heart, and liver, as well as paired tumor and non-tumor liver. As opposed to an indiscriminate stochastic process, we find pronounced demethylation of young long interspersed element 1 (LINE-1) retrotransposons in cancer, often distinct to the adjacent genome and other TEs. SINE-VNTR-Alu (SVA) retrotransposons, including their internal tandem repeat-associated CpG island, are near-universally methylated. We encounter allele-specific TE methylation and demethylation of aberrantly expressed young LINE-1s in normal tissues. Finally, we recover the complete sequences of tumor-specific LINE-1 insertions and their retrotransposition hallmarks, demonstrating how long-read sequencing can simultaneously survey the epigenome and detect somatic TE mobilization.enAluLINE-1SVAmethylationnanoporeretrotransposonDNA MethylationDNA Transposable ElementsDNA, NeoplasmEpigenesis, GeneticEpigenomeFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLong Interspersed Nucleotide ElementsMiddle AgedNanopore SequencingNeoplasmsOrgan Specificityresearch article33186547open access10.1016/j.molcel.2020.10.0241097-4164http://www.cell.com/article/S1097276520307310/pdf