ArticleNucleic acids research2007
A novel E4BP4 element drives circadian expression of mPeriod2.
Article in Nucleic acids research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 101 citations in OpenAlex.
- Intracrine androgen metabolism in the meibomian gland: regulation, circadian control, and implications in dry eye disease.Endocrine journal · 2026Review
- D-Box Binding Protein (DBP) as a Circadian Output Regulator: Molecular Mechanisms, Tissue-Specific Functions, and Disease Relevance.International journal of molecular sciences · 2026Review
- The transcription factor NFIL3 drives innate lymphoid cell specification from lymphoid progenitors.Immunity · 2025Article
- Pretreatment of Mice with 830 nm Light Enhances Endurance During Acute Exercise.Muscles (Basel, Switzerland) · 2025Article
- Feeding regime synchronizes circadian clock in choroid plexus - insight into a complex mechanism.Cellular and molecular life sciences : CMLS · 2025Article
- Identification of angiotensin II-responsive circadian clock gene expression in adrenal zona glomerulosa cells and human adrenocortical H295R cells.Frontiers in endocrinology · 2025Article
- The circadian clock in enamel development.International journal of oral science · 2024Review
- Timeless noncoding DNA contains cell-type preferential enhancers important for proper Drosophila circadian regulation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The role of basic leucine zipper transcription factor E4BP4 in cancer: a review and update.Molecular biology reports · 2024Review
- PER2 integrates circadian disruption and pituitary tumorigenesis.Theranostics · 2023Article
- E4BP4 Coordinates Circadian Control of Cognition in Delirium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- A wrinkle in time: circadian biology in pulmonary vascular health and disease.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Different levels of circadian (de)synchrony -- where does it hurt?F1000Research · 2022Review
- Comparative transcriptome analysis and CRISPR/Cas9 gene editing reveal that E4BP4 mediates lithium upregulation ofOpen biology · 2021Article
- Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism.Endocrinology · 2021Review
- Introduction to the Clock System.Advances in experimental medicine and biology · 2021Article
- Circadian Clock Regulates Inflammation and the Development of Neurodegeneration.Frontiers in cellular and infection microbiology · 2021Review
- After-Effects of Time-Restricted Feeding on Whole-Body Metabolism and Gene Expression in Four Different Peripheral Tissues.Obesity (Silver Spring, Md.) · 2020Article
- Role of Non-Coding RNAs in Lung Circadian Clock Related Diseases.International journal of molecular sciences · 2020Review
- Single-cell in vivo imaging of cellular circadian oscillators in zebrafish.PLoS biology · 2020Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Period2 (Per2) is an essential component of the mammalian clock mechanism and robust circadian expression of Per2 is essential for the maintenance of circadian rhythms. Although recent studies have shown that the circadian E2 enhancer (a non-canonical E-box) accounts for most of the circadian transcriptional drive of mPer2, little is known about the other cis-elements of mPer2 oscillatory transcription. Here, we examined the contribution of E4BP4 to Per2 mRNA oscillation in the cell-autonomous clock. Knockdown experiments of E4BP4 in both Northern blots and real-time luciferase assays suggested that endogenous E4BP4 negatively regulates Per2 mRNA oscillation. Sequence analysis revealed two putative E4BP4-binding sites (termed A-site and B-site) on mammalian Per2 promoter regions. Luciferase assays with mutant constructs showed that a novel E4BP4-binding site (B-site) is responsible for E4BP4-mediated transcriptional repression of Per2. Furthermore, chromatin immunoprecipitation assays in vivo showed that the peak of E4BP4 binding to the B-site on the Per2 promoter almost matched the trough of Per2 mRNA expression. Importantly, real-time luciferase assays showed that the B-site in addition to the E2 enhancer is required for robust circadian expression of Per2 in the cell-autonomous clock. These findings indicated that E4BP4 is required for the negative regulation of mammalian circadian clocks.
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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.