%0 Journal Article
%A Ewing, Adam D
%A Smits, Nathan
%A Sanchez-Luque, Francisco J
%A Faivre, Jamila
%A Brennan, Paul M
%A Richardson, Sandra R
%A Cheetham, Seth W
%A Faulkner, Geoffrey J
%T Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling.
%D 2020
%U http://hdl.handle.net/10668/16598
%X Transposable 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.
%K Alu
%K LINE-1
%K SVA
%K methylation
%K nanopore
%K retrotransposon
%~