RT Journal Article
T1 Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling.
A1 Ewing, Adam D
A1 Smits, Nathan
A1 Sanchez-Luque, Francisco J
A1 Faivre, Jamila
A1 Brennan, Paul M
A1 Richardson, Sandra R
A1 Cheetham, Seth W
A1 Faulkner, Geoffrey J
K1 Alu
K1 LINE-1
K1 SVA
K1 methylation
K1 nanopore
K1 retrotransposon
AB 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.
YR 2020
FD 2020-11-12
LK http://hdl.handle.net/10668/16598
UL http://hdl.handle.net/10668/16598
LA en
DS RISalud
RD Apr 14, 2025