Transcriptional perturbation of LINE-1 elements reveals their cis-regulatory potential

Long interspersed element-1 (LINE-1 or L1) retrotransposons constitute the largest transposable element (TE) family in mammalian genomes and contribute prominently to inter- and intra-individual genetic variation. Although most L1 elements are inactive, some evolutionary younger elements remain inta...

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Published inbioRxiv
Main Authors Pérez-Rico, Yuvia A, Bousard, Aurélie, Lenka Henao Misikova, Eskeatnaf Mulugeta, De Almeida, Sergio F, Muotri, Alysson R, Heard, Edith, Anne-Valerie Gendrel
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 20.02.2024
Subjects
Embryo cells
Gene expression
Gene silencing
Genes
Genetic diversity
Genomes
Long interspersed nucleotide elements
Retrotransposition
Stem cells
Transcription activation
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Summary:Long interspersed element-1 (LINE-1 or L1) retrotransposons constitute the largest transposable element (TE) family in mammalian genomes and contribute prominently to inter- and intra-individual genetic variation. Although most L1 elements are inactive, some evolutionary younger elements remain intact and genetically competent for transcription and occasionally retrotransposition. Despite being generally more abundant in gene-poor regions, intact or full-length L1s (FL-L1) are also enriched around specific classes of genes and on the eutherian X chromosome. How proximal FL-L1 may affect nearby gene expression remains unclear. In this study, we aim to examine this in a systematic manner using engineered mouse embryonic stem cells (ESCs) where the expression of one representative active L1 subfamily is specifically perturbed. We found that ~1,024 genes are misregulated following FL-L1 activation and to a lesser extent (~81 genes), following their repression. In most cases (68%), misexpressed genes contain an intronic FL-L1 or lie near a FL-L1 (<260 kb). Gene ontology analysis shows that upon L1 activation, up-regulated genes are enriched for neuronal function-related terms, suggesting that some L1 elements may have evolved to control neuronal gene networks. These results illustrate the cis-regulatory impact of FL-L1 elements and suggest a broader role for L1s than originally anticipated.Competing Interest StatementThe authors have declared no competing interest.
DOI:10.1101/2024.02.20.581275