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Comprehensive locus-specific L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integration sites
| Content Provider | Hyper Articles en Ligne (HAL) |
|---|---|
| Author | Lanciano, Sophie Philippe, Claude Sarkar, Arpita Pratella, David Domrane, Cécilia Doucet, Aurélien Essen, Dominic Van Saccani, Simona Ferry, Laure Defossez, Pierre-Antoine Cristofari, Gael |
| Copyright Year | 2024 |
| Abstract | 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. |
| Related Links | https://hal.science/hal-04245960/file/2023.01.03.522582v3.full.pdf |
| DOI | 10.1101/2023.01.03.522582 |
| Language | English |
| Publisher | HAL CCSD |
| Access Restriction | Open |
| Subject Keyword | LINE-1 nanopore sequencing transcription factor genomic profiling mobile element insertion transcription L1 chromatin states mobile genetic element retrotransposition ESR1 transposon transposition YY1 methyl-cytosine L1 chimeric transcripts LCTs DNA methylation nuclear receptor transposable elements retrotransposon Molecular biology Life Sciences [q-bio] Biochemistry, Molecular Biology Quantitative Methods [q-bio.QM] Life Sciences [q-bio] Genetics Life Sciences [q-bio] Life Sciences [q-bio] Genomics [q-bio.GN] Life Sciences [q-bio] Cancer Life Sciences [q-bio] Human genetics |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology |
