Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling.
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.
['Ewing|Adam D|AD|', 'Smits|Nathan|N|', 'Sanchez-Luque|Francisco J|FJ|', 'Faivre|Jamila|J|', 'Brennan|Paul M|PM|', 'Richardson|Sandra R|SR|', 'Cheetham|Seth W|SW|', 'Faulkner|Geoffrey J|GJ|']
D019175:DNA Methylation D004251:DNA Transposable Elements D004273:DNA, Neoplasm D044127:Epigenesis, Genetic D000081122:Epigenome D005260:Female D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D006801:Humans D020084:Long Interspersed Nucleotide Elements D008875:Middle Aged D000081414:Nanopore Sequencing D009369:Neoplasms D009928:Organ Specificity
nanopore methylation LINE-1 retrotransposon SVA Alu