ArticleThe Journal of biological chemistry2011
Histone deacetylase (HDAC) activity is critical for embryonic kidney gene expression, growth, and differentiation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.Nature communications · 2019Pooled it
- Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity.American journal of human genetics · 2016Pooled it
- Epigenetic regulation of kidney development.Nature reviews. Nephrology · 2026Review
- Epigenetic regulation of nephrogenesis: from Waddington's landscape to adult disease.American journal of physiology. Renal physiology · 2026Review
- Local acetyl-CoA metabolism and acetate recycling as epigenetic regulators of chromatin dynamics.FEMS yeast research · 2026Review
- TET1 loss propels the development of hyperthyroidism by remodeling histone modifications of PAX8 promoter.Experimental & molecular medicine · 2025Article
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Epigenetic Regulation in Wilms Tumor.Biomedicines · 2025Review
- Loss of Notch dimerization perturbs intestinal homeostasis by a mechanism involving HDAC activity.PLoS genetics · 2024Article
- Epigenetic DNA Methylation and Protein Homocysteinylation: Key Players in Hypertensive Renovascular Damage.International journal of molecular sciences · 2024Review
- Unlocking the epigenetic symphony: histone acetylation's impact on neurobehavioral change in neurodegenerative disorders.Epigenomics · 2024Review
- Repurposed drugs as histone deacetylase 8 inhibitors: Implications in cancer and neuropathological conditions.Frontiers in pharmacology · 2024Article
- The function of miRNAs in the process of kidney development.Non-coding RNA research · 2023Review
- Dually Modified Cellulose as a Non-Viral Vector for the Delivery and Uptake of HDAC3 siRNA.Pharmaceutics · 2023Article
- Sex-specific epigenetic programming in renal fibrosis and inflammation.American journal of physiology. Renal physiology · 2023Review
- The Pleiotropic Effects of Fumarate: From Mitochondrial Respiration to Epigenetic Rewiring and DNA Repair Mechanisms.Metabolites · 2023Review
- The Role of Epigenetics in Neuroinflammatory-Driven Diseases.International journal of molecular sciences · 2022Review
- Bim Expression Modulates Branching Morphogenesis of the Epithelium and Endothelium.Biomolecules · 2022Article
- Are Alterations in DNA Methylation Related to CKD Development?International journal of molecular sciences · 2022Review
- Role of Canonical Wnt/β-Catenin Pathway in Regulating Chondrocytic Hypertrophy in Mesenchymal Stem Cell-Based Cartilage Tissue Engineering.Frontiers in cell and developmental biology · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Histone deacetylases (HDACs) regulate fundamental biological processes such as cellular proliferation, differentiation, and survival via genomic and nongenomic effects. This study examined the importance of HDAC activity in the regulation of gene expression and differentiation of the developing mouse kidney. Class I HDAC1-3 and class II HDAC4, -7, and -9 genes are developmentally regulated. Moreover, HDAC1-3 are highly expressed in nephron precursors. Short term treatment of cultured mouse embryonic kidneys with HDAC inhibitors (HDACi) induced global histone H3 and H4 hyperacetylation and H3K4 hypermethylation. However, genome-wide profiling revealed that the HDAC-regulated transcriptome is restricted and encompasses regulators of the cell cycle, Wnt/β-catenin, TGF-β/Smad, and PI3K-AKT pathways. Further analysis demonstrated that base-line expression of key developmental renal regulators, including Osr1, Eya1, Pax2/8, WT1, Gdnf, Wnt9b, Sfrp1/2, and Emx2, is dependent on intact HDAC activity. Treatment of cultured embryonic kidney cells with HDACi recapitulated these gene expression changes, and chromatin immunoprecipitation assays revealed that HDACi is associated with histone hyperacetylation of Pax2/Pax8, Gdnf, Sfrp1, and p21. Gene knockdown studies demonstrated that HDAC1 and HDAC2 play a redundant role in regulation of Pax2/8 and Sfrp1 but not Gdnf. Long term treatment of embryonic kidneys with HDACi impairs the ureteric bud branching morphogenesis program and provokes growth arrest and apoptosis. We conclude that HDAC activity is critical for normal embryonic kidney homeostasis, and we implicate class I HDACs in the regulation of early nephron gene expression, differentiation, and survival.
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Registered trials
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.