About L1
LINE-1 (L1) retrotransposons represent an abundant and repetitive fraction of the human genome and are potent endogenous mutagens. Epigenetic mechanisms suppress their activity in most somatic tissues, but they are transcribed and eventually mobilized in the early embryo, in the brain and in many cancers (
Faulkner and Garcia-Perez 2017 ;
Payer and Burns 2019). Consistently, loss of bulk L1 DNA methylation is a common cancer biomarker, and demethylating agents used in cancer therapy further increase L1 expression. However, L1 sequences are heterogeneous as they encompass several families of different evolutionary age, and are highly dispersed, each copy being differently affected by its genomic environment.
To individually measure the DNA methylation levels of each full-length L1 copy inserted in the genome, we adapted to bisulfite-treated DNA the ATLAS-seq approach, a method originally developed to map L1 elements in the human genome. This strategy, termed bisulfite-ATLAS sequencing (bs-ATLAS-seq, see
here, for further information), provides both the location of L1 insertions and the methylation state of the most distal 210 bp of their promoter. Importantly, these data are obtained both for reference and non-reference insertions. Although bs-ATLAS-seq was designed to comprehensively catch the most recent and human-specific L1 elements (L1HS) as they form the only autonomously active transposable element family in humans, bs-ATLAS-seq also recovers a significant fraction of other young primate-specific L1 families (L1PA2 to L1PA8).
The proportion of methylated CpG (mCG) at each site and the frequency of each methylation pattern deduced from single reads can be obtained for are indicated on the charts (right). Single-nucleotide and single-molecule data are available: (i) for each individual insertion in Methylation data tab or (ii) for all detected L1 insertion for a given cell line in Cell lines tab. For non-reference elements the positions of CpGs are related to L1HS consensus sequence and for reference elements the positions are related to the genomic coordinates.