ArticleBMC genomics2013
Cubilin expression is monoallelic and epigenetically augmented via PPARs.
Article in BMC genomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Gene Expression in Urinary Sediment Cells as an Indicator of the Contribution of Plasma Lipids to Diabetic Kidney Disease.Journal of diabetes research · 2025Article
- Locus specific epigenetic modalities of random allelic expression imbalance.Nature communications · 2021Article
- X-Chromosome Inactivation and Autosomal Random Monoallelic Expression as "Faux Amis".Frontiers in cell and developmental biology · 2021Review
- Participation of the SMAD2/3 signalling pathway in the down regulation of megalin/LRP2 by transforming growth factor beta (TGF-ß1).PloS one · 2019Article
- Allele-specific RNA imaging shows that allelic imbalances can arise in tissues through transcriptional bursting.PLoS genetics · 2019Article
- The Benefits of Tubular Proteinuria: An Evolutionary Perspective.Journal of the American Society of Nephrology : JASN · 2018Article
- Differentiation of cardiomyocytes from amniotic fluid‑derived mesenchymal stem cells by combined induction with transforming growth factor β1 and 5‑azacytidine.Molecular medicine reports · 2017Article
- Distinct intestinal adaptation for vitamin B12 and bile acid absorption revealed in a new mouse model of massive ileocecal resection.Biology open · 2017Article
- Perspective: Is Random Monoallelic Expression a Contributor to Phenotypic Variability of Autosomal Dominant Disorders?Frontiers in genetics · 2017Article
- Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.Journal of the American Society of Nephrology : JASN · 2016Article
- Random monoallelic expression: regulating gene expression one allele at a time.Trends in genetics : TIG · 2014Review
- Cubilin maintains blood levels of HDL and albumin.Journal of the American Society of Nephrology : JASN · 2014Article
- Random monoallelic gene expression increases upon embryonic stem cell differentiation.Developmental cell · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCubilin is an endocytic receptor that is necessary for renal and intestinal absorption of a range of ligands. Endocytosis mediated by cubilin and its co-receptor megalin is the principal mechanism for proximal tubule reabsorption of proteins from the glomerular filtrate. Cubilin is also required for intestinal endocytosis of intrinsic factor-vitamin B12 complex. Despite its importance, little is known about the regulation of cubilin expression.
resultsHere we show that cubilin expression is under epigenetic regulation by at least two processes. The first process involves inactivation of expression of one of the cubilin alleles. This monoallelic expression state could not be transformed to biallelic by inhibiting DNA methylation or histone deacetylation. The second process involves transcriptional regulation of cubilin by peroxisome proliferator-activated receptor (PPAR) transcription factors that are themselves regulated by DNA methylation and histone deacetylation. This is supported by findings that inhibitors of DNA methylation and histone deacetylation, 5Aza and TSA, increase cubilin mRNA and protein in renal and intestinal cell lines. Not only was the expression of PPARα and γ inducible by 5Aza and TSA, but the positive effects of TSA and 5Aza on cubilin expression were also dependent on both increased PPAR transcription and activation. Additionally, 5Aza and TSA had similar effects on the expression of the cubilin co-receptor, megalin.
conclusionsTogether, these findings reveal that cubilin and megalin mRNA expression is under epigenetic control and thus point to new avenues for overcoming pathological suppression of these genes through targeting of epigenetic regulatory processes.
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