ArticleKidney international2023
Enhancer and super-enhancer landscape in polycystic kidney disease.
Article in Kidney international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 25 citations in OpenAlex.
- Disruption of a six-nucleotide miRNA motif improves PKD1 dosage and ameliorates polycystic kidney disease.Nucleic acids research · 2026Article
- Super enhancer-driven LINC01013 mediates hypoxia-induced mitochondrial dysfunction by HSPA9 to determine pulmonary arterial smooth muscle cell fate.Cellular and molecular life sciences : CMLS · 2026Article
- Disruption of a six-nucleotide miRNA motif improvesbioRxiv : the preprint server for biology · 2025Article
- LNP-enclosed NamiRNA inhibits pancreatic cancer proliferation and migration via dual pathways.Journal of nanobiotechnology · 2025Article
- Targeting super-enhancers in liver cancer: from pathogenic mechanisms to clinical applications.Frontiers in pharmacology · 2025Review
- Sexually dimorphic renal expression of mouse Klotho is directed by a kidney-specific distal enhancer responsive to HNF1b.Communications biology · 2024Article
- Myocardin-Related Transcription Factor Mediates Epithelial Fibrogenesis in Polycystic Kidney Disease.Cells · 2024Article
- Cross-Species Insights into Autosomal Dominant Polycystic Kidney Disease: Provide an Alternative View on Research Advancement.International journal of molecular sciences · 2024Review
- Sexually dimorphic renal expression ofResearch square · 2024Article
- Defects of renal tubular homeostasis and cystogenesis in theiScience · 2024Article
- The chromatin landscape of healthy and injured cell types in the human kidney.Nature communications · 2024Article
- Targeting the ADPKD methylome using nanoparticle-mediated combination therapy.APL bioengineering · 2023Article
- Mechanisms of Cyst Development in Polycystic Kidney Disease.Advances in kidney disease and health · 2023Review
- A body map of super-enhancers and their function in pig.Frontiers in veterinary science · 2023Article
- Decorating Histones in Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2022Article
- PKD1 and PKD2 mRNA cis-inhibition drives polycystic kidney disease progression.Nature communications · 2022Article
- Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease.Molecules (Basel, Switzerland) · 2022Article
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7 authors at 2 institutions in 1 country.
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Abstract
Widespread aberrant gene expression is a pathological hallmark of polycystic kidney disease (PKD). Numerous pathogenic signaling cascades, including c-Myc, Fos, and Jun, are transactivated. However, the underlying epigenetic regulators are poorly defined. Here we show that H3K27ac, an acetylated modification of DNA packing protein histone H3 that marks active enhancers, is elevated in mouse and human samples of autosomal dominant PKD. Using comparative H3K27ac ChIP-Seq analysis, we mapped over 16000 active intronic and intergenic enhancer elements in Pkd1-mutant mouse kidneys. We found that the cystic kidney epigenetic landscape resembles that of a developing kidney, and over 90% of upregulated genes in Pkd1-mutant kidneys are co-housed with activated enhancers in the same topologically associated domains. Furthermore, we identified an evolutionarily conserved enhancer cluster downstream of the c-Myc gene and super-enhancers flanking both Jun and Fos loci in mouse and human models of autosomal dominant PKD. Deleting these regulatory elements reduced c-Myc, Jun, or Fos abundance and suppressed proliferation and 3D cyst growth of Pkd1-mutant cells. Finally, inhibiting glycolysis and glutaminolysis or activating Ppara in Pkd1-mutant cells lowerd global H3K27ac levels and its abundance on c-Myc enhancers. Thus, our work suggests that epigenetic rewiring mediates the transcriptomic dysregulation in PKD, and the regulatory elements can be targeted to slow cyst growth.
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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 OpenQuestion graph.