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09:20
CRISPR-Mediated Reorganization of Chromatin Loop Structure
Published on: September 14, 2018
Cubilin expression is monoallelic and epigenetically augmented via PPARs
Obaidullah Aseem1, Jeremy L Barth, Sandra C Klatt
1Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
BMC Genomics
|June 19, 2013
Summary
Cubilin (CUB) and megalin (LRP2) gene expression is epigenetically regulated. DNA methylation and histone deacetylation influence CUB and LRP2 expression via PPAR transcription factors.
Area of Science:
- Molecular Biology
- Epigenetics
- Cell Biology
Background:
- Cubilin (CUB) is an endocytic receptor crucial for nutrient absorption in the kidneys and intestines.
- CUB and its co-receptor megalin (LRP2) mediate protein reabsorption in renal proximal tubules and vitamin B12 uptake in the intestine.
- Regulation of CUB expression remains largely unknown despite its functional significance.
Purpose of the Study:
- To investigate the epigenetic regulation of cubilin (CUB) expression.
- To explore the role of DNA methylation and histone deacetylation in controlling CUB and megalin (LRP2) expression.
- To identify the transcription factors involved in CUB regulation.
Main Methods:
- Utilized cell lines to study CUB and LRP2 expression.
- Applied inhibitors of DNA methylation (5-aza) and histone deacetylation (TSA).
- Assessed mRNA and protein levels of CUB, LRP2, and peroxisome proliferator-activated receptors (PPARs).
Main Results:
- Cubilin expression is regulated epigenetically, involving monoallelic expression.
- Inhibitors of DNA methylation and histone deacetylation (5-aza, TSA) increased CUB mRNA and protein.
- PPARα and PPARγ expression were induced by 5-aza and TSA, and their activation was necessary for increased CUB expression.
- MEGALIN expression was also upregulated by 5-aza and TSA.
Conclusions:
- Cubilin and megalin (LRP2) mRNA expression are under epigenetic control.
- Epigenetic mechanisms, including DNA methylation and histone deacetylation, influence CUB and LRP2 expression through PPAR transcription factors.
- Targeting epigenetic processes offers potential therapeutic strategies for conditions with suppressed CUB and LRP2 expression.
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