Comprehensive locus-specific L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integration sites
Résumé
Long interspersed element-1 (L1) retrotransposons play important roles in human disease and evolution. Their global activity is repressed by DNA methylation, but studying the regulation of individual copies has been difficult. Here, we combine short- and long-read sequencing to resolve the DNA methylation profiles of these repeated sequences in a panel of normal and cancer cells genome-wide at single-locus resolution. We unveil key principles underpinning L1 methylation heterogeneity among cell-types, families and integration sites. First, intronic L1 methylation is intimately associated with gene transcription. Conversely, L1s can influence the methylation status of the upstream region over short distances (300 bp). This phenomenon is accompanied by the binding of specific transcription factors, which drive the expression of L1 and chimeric transcripts. Finally, L1 hypomethylation alone is generally insufficient to trigger L1 expression due to redundant silencing pathways. Our results illuminate the epigenetic and transcriptional interplay between retrotransposons and their host genome.
Mots clés
LINE-1
L1
transposable elements
mobile genetic element
transposon
transposition
retrotransposon
retrotransposition
mobile element insertion
DNA methylation
methyl-cytosine
nanopore sequencing
chromatin states
transcription
L1 chimeric transcripts
LCTs
YY1
ESR1
transcription factor
nuclear receptor
genomic profiling
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