ArticleNature structural & molecular biology2024
Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Insights into X-linked Dystonia-Parkinsonism and Spinocerebellar Ataxia type 36 Through the Lens of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.Molecular neurobiology · 2026Review
- Activation of transposable elements is linked to a region- and cell type-specific interferon response in Parkinson's disease.Science advances · 2026Article
- Review
- Review
- Correction of the molecular phenotype of X-linked Dystonia-Parkinsonism reveals a non-canonical function of BRD4.Nature communications · 2026Article
- Complementary constraints in germ and immune cells shape evolution of gene regulation and phenotype.bioRxiv : the preprint server for biology · 2026Article
- The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements.Nature genetics · 2026Review
- Loss of SETDB1-mediated H3K9me3 in human neural progenitor cells leads to transcriptional activation of L1 retrotransposons.Nucleic acids research · 2026Article
- MER57E3 transposable elements regulate gene expression in a human cell model of neural development.Genome biology · 2026Article
- Retroviral insertions contributed to the divergence of human and chimpanzee brains.bioRxiv : the preprint server for biology · 2025Article
- Article
- Therapeutic targeting of alternative splicing caused by a lethal noncoding structural variant in X-linked dystonia parkinsonism.medRxiv : the preprint server for health sciences · 2025Article
- Genome writing to dissect consequences of SVA retrotransposon disease X-Linked Dystonia Parkinsonism.bioRxiv : the preprint server for biology · 2025Article
- The arms race of ray-finned fish against the derepression of LTR retroelements.Scientific reports · 2024Article
- G-quadruplexes in an SVA retrotransposon cause aberrant TAF1 gene expression in X-linked dystonia parkinsonism.Nucleic acids research · 2024Article
- ZNF91 is an endogenous repressor of the molecular phenotype associated with X-linked dystonia-parkinsonism (XDP).Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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13 authors.
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Abstract
SVA (SINE (short interspersed nuclear element)-VNTR (variable number of tandem repeats)-Alu) retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at the TAF1 locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate the cis-regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increased TAF1 intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized and how their regulatory impact is constrained by an innate epigenetic defense system.
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