ArticlePLoS genetics2022
Genomic features underlie the co-option of SVA transposons as cis-regulatory elements in human pluripotent stem cells.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Transcriptional perturbation of LINE-1 elements reveals their cis-regulatory potential.EMBO reports · 2026Article
- Transposable elements impact the human regulatory landscape through cell type specific epigenomic associations.Nature communications · 2026Article
- Transposable Elements Seed Transcription Factor Binding Sites to Sequence-Specific Double-Stranded DNA Binding TF Networks Contributing to Governance of Primate Brain Evolution.Journal of molecular evolution · 2026Article
- Hominoid-specific transposable elements reshaped neural crest migration in craniofacial development.Molecular systems biology · 2025Article
- Variability of transposable elements in six genetic isolates from North-Eastern Italy and their relationship with alcohol consumption, tobacco use and BMI.BMC genomics · 2025Article
- Transposable elements may enhance antiviral resistance in HIV-1 elite controllers.Genome biology · 2025Article
- Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer's disease.Nature communications · 2025Article
- YY1 is a transcriptional activator of the mouse LINE-1 Tf subfamily.Nucleic acids research · 2024Article
- Epigenomic insights into common human disease pathology.Cellular and molecular life sciences : CMLS · 2024Review
- A SINE-VNTR-Alu at the LRIG2 locus is associated with proximal and distal gene expression in CRISPR and population models.Scientific reports · 2024Article
- YY1 is a transcriptional activator of mouse LINE-1 Tf subfamily.bioRxiv : the preprint server for biology · 2024Article
- Transposable elements may enhance antiviral resistance in HIV-1 elite controllers.bioRxiv : the preprint server for biology · 2023Article
- Regulation of expression quantitative trait loci by SVA retrotransposons within the major histocompatibility complex.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Polygenic burden of short tandem repeat expansions promote risk for Alzheimer's disease.medRxiv : the preprint server for health sciences · 2023Article
- Repetitive DNA sequence detection and its role in the human genome.Communications biology · 2023Review
- Genetic features and genomic targets of human KRAB-zinc finger proteins.Genome research · 2023Article
- R-loop landscape in mature human sperm: Regulatory and evolutionary implications.Frontiers in genetics · 2023Article
- RDA coupled with deep sequencing detects somatic SVA-retrotranspositions and mosaicism in the human brain.Frontiers in cell and developmental biology · 2023Article
- Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors.Development (Cambridge, England) · 2022Article
- The Role of Transposable Elements of the Human Genome in Neuronal Function and Pathology.International journal of molecular sciences · 2022Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as functional enhancers while others are not are underappreciated. SINE-VNTR-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-specific. Many studies indicate that SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such processes have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication into human stem-cell gene regulation. We found that ~750 SVAs are co-opted as functional cis-regulatory elements in human induced pluripotent stem cells. These SVAs are significantly closer to genes and harbor more transcription factor binding sites than non-co-opted SVAs. We show that a long DNA motif composed of flanking YY1/2 and OCT4 binding sites is enriched in the co-opted SVAs and that these two transcription factors bind consecutively on the TE sequence. We used CRISPRi to epigenetically repress active SVAs in stem cell-like NCCIT cells. Epigenetic perturbation of active SVAs strongly attenuated YY1/OCT4 binding and influenced neighboring gene expression. Ultimately, SVA repression resulted in ~3,000 differentially expressed genes, 131 of which were the nearest gene to an annotated SVA. In summary, we demonstrated that SVAs modulate human gene expression, and uncovered that location and sequence composition contribute to SVA domestication into gene regulatory networks.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.