ArticleNature communications2025
Switch-like gene expression modulates disease risk.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Genomes From 117 Vertebrate Species Reveal Rapidly Evolving Segmental-Duplication Landscapes.Genome biology and evolution · 2026Article
- Comparative Transcriptomics Suggests that Breast Secretory Epithelium Reuses Gene Repertoires Conserved Across Vertebrates Beyond Mammals.Genome biology and evolution · 2026Article
- Liver progenitor cells perform wound healing in a scratch assay by concerted bistable circuits.NPJ systems biology and applications · 2026Article
- Leveraging the germ layer development patterns to predict prognosis and identify MEST as a novel therapeutic target in glioma.Cancer cell international · 2026Article
- Genetic and functional evidence implicates amedRxiv : the preprint server for health sciences · 2025Article
- Metabolic Memory Following Metabolic Bariatric Surgery: Mechanisms, Clinical Implications, and Strategies for Long-Term Success.Obesity surgery · 2025Review
- Genomes from 117 vertebrate species reveal rapidly evolving segmental duplication landscapes.bioRxiv : the preprint server for biology · 2025Article
- Read mismapping from segmental duplications drives spuriousbioRxiv : the preprint server for biology · 2025Article
- Switch-like gene expression modulates disease risk.Nature communications · 2025Article
- Energy landscape analysis based on the Ising model: Tutorial review.PLOS complex systems · 2025Article
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9 authors.
Funding
Abstract
While switch-like gene expression ("on" in some individuals and "off" in others) has been linked to biological variation and disease susceptibility, a systematic analysis across tissues is lacking. Here, we analyze genomes, transcriptomes, and methylomes from 943 individuals across 27 tissues, identifying 473 switch-like genes. The identified genes are enriched for associations with cancers and immune, metabolic, and skin diseases. Only 40 (8.5%) switch-like genes show genetically controlled switch-like expression in all tissues, i.e., universally switch-like expression. The rest show switch-like expression in specific tissues. Methylation analysis suggests that genetically driven epigenetic silencing explains the universally switch-like pattern, whereas hormone-driven epigenetic modification likely underlies the tissue-specific pattern. Notably, tissue-specific switch-like genes tend to be switched on or off in unison within individuals, driven by tissue-specific master regulators. In the vagina, we identified seven concordantly switched-off genes linked to vaginal atrophy in females. Experimental analysis of vaginal tissues shows that low estrogen levels lead to decreased epithelial thickness and ALOX12 expression. We propose that switched-off driver genes in basal and parabasal epithelia suppress cell proliferation, leading to epithelial thinning and vaginal atrophy. Our findings underscore the implications of switch-like genes for diagnostic and personalized therapeutic applications.
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