ArticleThe Journal of biological chemistry2014
Epigenetic modulation of intestinal cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) gene expression by DNA methylation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation.MedScience · 2026Article
- DNA methylation profiling reveals novel pathway implicated in cardiovascular diseases of diabetes.Frontiers in endocrinology · 2023Article
- Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.Signal transduction and targeted therapy · 2022Review
- Cholesterol sulfate alleviates ulcerative colitis by promoting cholesterol biosynthesis in colonic epithelial cells.Nature communications · 2022Article
- Inhibition of NPC1L1 disrupts adaptive responses of drug-tolerant persister cells to chemotherapy.EMBO molecular medicine · 2022Article
- Genetic Determinants of Plasma Low-Density Lipoprotein Cholesterol Levels: Monogenicity, Polygenicity, and "Missing" Heritability.Biomedicines · 2021Review
- Differential DNA methylation in familial hypercholesterolemia.EBioMedicine · 2020Article
- Mechanisms of Niemann-Pick type C1 Like 1 protein degradation in intestinal epithelial cells.American journal of physiology. Cell physiology · 2019Article
- Epigenetic modulation of intestinal NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Molecular mechanism(s) involved in differential expression of vitamin C transporters along the intestinal tract.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Revisiting Human Cholesterol Synthesis and Absorption: The Reciprocity Paradigm and its Key Regulators.Lipids · 2016Review
- Lower Methylation of the ANGPTL2 Gene in Leukocytes from Post-Acute Coronary Syndrome Patients.PloS one · 2016Article
- Mechanism(S) Involved in the Colon-Specific Expression of the Thiamine Pyrophosphate (Tpp) Transporter.PloS one · 2016Article
- Epigenetic regulation of cholesterol homeostasis.Frontiers in genetics · 2014Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Intestinal NPC1L1 transporter is essential for cholesterol absorption and the maintenance of cholesterol homeostasis in the body. NPC1L1 is differentially expressed along the gastrointestinal tract with very low levels in the colon as compared with the small intestine. This study was undertaken to examine whether DNA methylation was responsible for segment-specific expression of NPC1L1. Treatment of mice with 5-azacytidine (i.p.) resulted in a significant dose-dependent increase in NPC1L1 mRNA expression in the colon. The lack of expression of NPC1L1 in the normal colon was associated with high levels of methylation in the area flanking the 3-kb fragment upstream of the initiation site of the mouse NPC1L1 gene in mouse colon as analyzed by EpiTYPER® MassARRAY®. The high level of methylation in the colon was observed in specific CpG dinucleotides and was significantly decreased in response to 5-azacytidine. Similar to mouse NPC1L1, 5-azacytidine treatment also increased the level of human NPC1L1 mRNA expression in the intestinal HuTu-80 cell line in a dose- and time-dependent manner. Silencing the expression of DNA methyltransferase DNMT1, -2, -3A, and -3B alone by siRNA did not affect NPC1L1 expression in HuTu-80 cells. However, the simultaneous attenuation of DNMT1 and -3B expression caused a significant increase in NPC1L1 mRNA expression as compared with control. Also, in vitro methylation of the human NPC1L1 promoter significantly decreased NPC1L1 promoter activity in human intestinal Caco2 cells. In conclusion, our data demonstrated for the first time that DNA methylation in the promoter region of the NPC1L1 gene appears to be a major mechanism underlying differential expression of NPC1L1 along the length of the gastrointestinal tract.
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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.