ArticleMobile DNA2021
Unbiased proteomic mapping of the LINE-1 promoter using CRISPR Cas9.
Article in Mobile DNA, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 11 citations in OpenAlex.
- LINE-1 retrotransposons: Multifaceted functions and regulatory mechanisms in health and disease.Molecular therapy. Nucleic acids · 2026Review
- In Depth Characterization of the Promoter Proximal Proteome of Single Copy Locus FOXP2.Molecular & cellular proteomics : MCP · 2026Article
- Human cGAS Drives LINE-1 Transcriptional Activation to Trigger MAVS-Dependent Cellular Senescence.Aging cell · 2026Article
- Multi-ancestry GWAS reveals loci linked to human variation in LINE-1- and Alu-insertion numbers.bioRxiv : the preprint server for biology · 2025Article
- Multi-ancestry GWAS reveals loci linked to human variation in LINE-1- and Alu-insertion numbers.Translational medicine of aging · 2025Article
- PRC1.6 localizes on chromatin with the human silencing hub (HUSH) complex for promoter-specific silencing.bioRxiv : the preprint server for biology · 2024Article
- An eQTL-based approach reveals candidate regulators of LINE-1 RNA levels in lymphoblastoid cells.PLoS genetics · 2024Article
- Regulation and function of transposable elements in cancer genomes.Cellular and molecular life sciences : CMLS · 2024Review
- Activation of Young LINE-1 Elements by CRISPRa.International journal of molecular sciences · 2023Article
- An eQTL-based Approach Reveals Candidate Regulators of LINE-1 RNA Levels in Lymphoblastoid Cells.bioRxiv : the preprint server for biology · 2023Article
- Research progress of LINE-1 in the diagnosis, prognosis, and treatment of gynecologic tumors.Frontiers in oncology · 2023Review
- Subfamily-specific differential contribution of individual monomers and the tether sequence to mouse L1 promoter activity.Mobile DNA · 2022Article
- Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe autonomous retroelement Long Interspersed Element-1 (LINE-1) mobilizes though a copy and paste mechanism using an RNA intermediate (retrotransposition). Throughout human evolution, around 500,000 LINE-1 sequences have accumulated in the genome. Most of these sequences belong to ancestral LINE-1 subfamilies, including L1PA2-L1PA7, and can no longer mobilize. Only a small fraction of LINE-1 sequences, approximately 80 to 100 copies belonging to the L1Hs subfamily, are complete and still capable of retrotransposition. While silenced in most cells, many questions remain regarding LINE-1 dysregulation in cancer cells.
resultsHere, we optimized CRISPR Cas9 gRNAs to specifically target the regulatory sequence of the L1Hs 5'UTR promoter. We identified three gRNAs that were more specific to L1Hs, with limited binding to older LINE-1 sequences (L1PA2-L1PA7). We also adapted the C-BERST method (dCas9-APEX2 Biotinylation at genomic Elements by Restricted Spatial Tagging) to identify LINE-1 transcriptional regulators in cancer cells. Our LINE-1 C-BERST screen revealed both known and novel LINE-1 transcriptional regulators, including CTCF, YY1 and DUSP1.
conclusionOur optimization and evaluation of gRNA specificity and application of the C-BERST method creates a tool for studying the regulatory mechanisms of LINE-1 in cancer. Further, we identified the dual specificity protein phosphatase, DUSP1, as a novel regulator of LINE-1 transcription.
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