ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Promoter methylation confers kidney-specific expression of the Klotho gene.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 83 citations in OpenAlex.
- Novel insights into the role of the renal interstitial microenvironment in Randall's plaque formation (Review).International journal of molecular medicine · 2026Review
- [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Epigenetic histone modifications in kidney disease and epigenetic memory.Clinical and experimental nephrology · 2025Review
- Role of DNA methylation transferase in urinary system diseases: From basic to clinical perspectives (Review).International journal of molecular medicine · 2025Review
- Inflammation-Induced Klotho Deficiency: A Possible Key Driver of Chronic Kidney Disease Progression.International journal of general medicine · 2025Review
- The aging heart: exploring the role of Klotho in cardiac health/function.The journal of cardiovascular aging · 2024Article
- A modular dCas9-based recruitment platform for combinatorial epigenome editing.Nucleic acids research · 2024Article
- Determination of the Relationship Between DNA Methylation Status ofBalkan journal of medical genetics : BJMG · 2023Article
- Dihydroartemisinin suppresses renal fibrosis in mice by inhibiting DNA-methyltransferase 1 and increasing Klotho.Acta pharmacologica Sinica · 2022Article
- Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly.Scientific reports · 2022Article
- Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease.Scientific reports · 2022Article
- Urine-Derived Stem Cell-Secreted Klotho Plays a Crucial Role in the HK-2 Fibrosis Model by Inhibiting the TGF-β Signaling Pathway.International journal of molecular sciences · 2022Article
- A Klotho-derived peptide protects against kidney fibrosis by targeting TGF-β signaling.Nature communications · 2022Article
- Inhibition of DNA methyltransferase aberrations reinstates antioxidant aging suppressors and ameliorates renal aging.Aging cell · 2022Article
- CCL5 Suppresses Klotho ExpressionFrontiers in physiology · 2022Article
- Phosphate and Cellular Senescence.Advances in experimental medicine and biology · 2022Article
- Klotho and Mesenchymal Stem Cells: A Review on Cell and Gene Therapy for Chronic Kidney Disease and Acute Kidney Disease.Pharmaceutics · 2021Review
- Epigenetic modifications of Klotho expression in kidney diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- PTSD and the klotho longevity gene: Evaluation of longitudinal effects on inflammation via DNA methylation.Psychoneuroendocrinology · 2020Article
- Serum Endocrine Fibroblast Growth Factors as Potential Biomarkers for Chronic Kidney Disease and Various Metabolic Dysfunctions in Aged Patients.Internal medicine (Tokyo, Japan) · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The aging suppressor geneKlotho is predominantly expressed in the kidney irrespective of species. Because Klotho protein is an essential component of an endocrine axis that regulates renal phosphate handling, the kidney-specific expression is biologically relevant; however, little is known about its underlying mechanisms. Here we provide in vitro and in vivo evidence indicating that promoter methylation restricts the expression of the Klotho gene in the kidney. Based on evolutionary conservation and histone methylation patterns, the region up to -1200 bp was defined as a major promoter element of the human Klotho gene. This region displayed promoter activity equally in Klotho-expressing and -nonexpressing cells in transient reporter assays, but the activity was reduced to ∼20% when the constructs were integrated into the chromatin in the latter. Both endogenous and transfected Klotho promoters were 30-40% methylated in Klotho-nonexpressing cells, but unmethylated in Klotho-expressing renal tubular cells. DNA demethylating agents increased Klotho expression 1.5- to 3.0-fold in nonexpressing cells and restored the activity of silenced reporter constructs. Finally, we demonstrated that a severe hypomorphic allele of Klotho had aberrant CpG methylation in kl/kl mice. These findings might be useful in therapeutic intervention for accelerated aging and several complications caused by Klotho down-regulation.
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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.