ArticleExperimental & molecular medicine2012
Circadian regulation of low density lipoprotein receptor promoter activity by CLOCK/BMAL1, Hes1 and Hes6.
Article in Experimental & molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Cryopreservation of siRNA-Treated Cells Is Feasible.Nucleic acid therapeutics · 2025Article
- Pan-cancer analysis reveals dual roles of HES6 in cancer immunity and prognosis.Discover oncology · 2025Article
- Alterations in Circadian Rhythms, Sleep, and Physical Activity in COVID-19: Mechanisms, Interventions, and Lessons for the Future.Molecular neurobiology · 2024Review
- Chronic Mealtime Shift Disturbs Metabolic and Urinary Functions in Mice: Effects of Daily Antioxidant Supplementation.International neurourology journal · 2024Article
- Archaic Introgression Shaped Human Circadian Traits.Genome biology and evolution · 2023Article
- Zinc Improves Semen Parameters in High-Fat Diet-Induced Male Rats by Regulating the Expression of LncRNA in Testis Tissue.Biological trace element research · 2023Article
- The Role of Biological Rhythms in New Drug Formulations to Cross the Brain Barriers.International journal of molecular sciences · 2023Review
- Associations of Dietary Intakes of Total and Specific Types of Fat with Blood Lipid Levels in the Filipino Women's Diet and Health Study (FiLWHEL).Global heart · 2023Article
- Chronic circadian desynchronization of feeding-fasting rhythm generates alterations in daily glycemia, LDL cholesterolemia and microbiota composition in mice.Frontiers in nutrition · 2023Article
- Profiling of circulating chromosome 21-encoded microRNAs, miR-155, and let-7c, in down syndrome.Molecular genetics & genomic medicine · 2022Article
- Chronic Cold Exposure Leads to Daytime Preference in the Circadian Expression of Hepatic Metabolic Genes.Frontiers in physiology · 2022Article
- Hepatic transcriptional responses to fasting and feeding.Genes & development · 2021Review
- Oscillating and stable genome topologies underlie hepatic physiological rhythms during the circadian cycle.PLoS genetics · 2021Article
- Disruptions of Circadian Rhythms and Thrombolytic Therapy During Ischemic Stroke Intervention.Frontiers in neuroscience · 2021Review
- Theabrownin from Pu-erh tea together with swinging exercise synergistically ameliorates obesity and insulin resistance in rats.European journal of nutrition · 2020Article
- Boolean function network analysis of time course liver transcriptome data to reveal novel circadian transcriptional regulators in mammals.Journal of the Chinese Medical Association : JCMA · 2019Article
- Article
- Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs).Scientific reports · 2017Article
- Using RNA sequencing to identify putative competing endogenous RNAs (ceRNAs) potentially regulating fat metabolism in bovine liver.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low density lipoprotein receptor (LDLR) plays an important role in the cholesterol homeostasis. We examined the possible circadian regulation of LDLR and mechanism(s) underlying it. In mice, blood glucose and plasma triglyceride, total and high density lipoprotein cholesterol varied distinctively throughout a day. In addition, LDLR mRNA oscillated in the liver in a functional clock-dependent manner. Accordingly, analysis of human LDLR promoter sequence revealed three putative E-boxes, raising the possible regulation of LDLR expression by E-box-binding transcription factors. To test this possibility, human LDLR promoter reporter constructs were transfected into HepG2 cells and the effects of CLOCK/BMAL1, Hes1, and Hes6 expression were analyzed. It was found that positive circadian transcription factor complex CLOCK/BMAL1 upregulated human LDLR promoter activity in a serum-independent manner, while Hes family members Hes1 and Hes6 downregulated it only under serum-depleted conditions. Both effects were mapped to proximal promoter region of human LDLR, where mutation or deletion of well-known sterol regulatory element (SRE) abolished only the repressive effect of Hes1. Interestingly, hes6 and hes1 mRNA oscillated in an anti-phasic manner in the wild-type but not in the per1-/-per2 -/- mouse. Comparative analysis of mouse, rat and human hes6 genes revealed that three E-boxes are conserved among three species. Transfection and site-directed mutagenesis studies with hes6 reporter constructs confirmed that the third E-box in the exon IV is functionally induced by CLOCK/BMAL1. Taken together, these results suggest that LDLR expression is under circadian control involving CLOCK/BMAL1 and Hes family members Hes1 and Hes6.
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