ArticleGenes & development2004
The loss of circadian PAR bZip transcription factors results in epilepsy.
Article in Genes & development, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
141 citing papers in PubMed, 1 synthesis or guideline pooled it, 280 citations in OpenAlex.
- Clock gene dysregulation in epilepsy: A systematic review.Epilepsia open · 2026Pooled it
- Review
- D-Box Binding Protein (DBP) as a Circadian Output Regulator: Molecular Mechanisms, Tissue-Specific Functions, and Disease Relevance.International journal of molecular sciences · 2026Review
- Chronic sleep deprivation promotes drug-resistant epilepsy via the BMAL1-mTOR-P-gp axis.Epilepsia open · 2026Article
- Reciprocal regulation between autism risk gene POGZ and circadian clock.JCI insight · 2026Article
- A temporal dialogue between the circadian clock and chronic inflammatory diseases.Disease models & mechanisms · 2026Review
- Photoreceptor control ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Circadian rhythms in pediatric neurocritical care: interfaces and opportunities.Frontiers in neurology · 2026Review
- Dissecting age-specific genetic architecture of vitiligo through integrative Post-GWAS analysis.Frontiers in immunology · 2026Article
- Daily liver rhythms: Coupling morphological and molecular oscillations.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Circadian clock communication during homeostasis and ageing.Nature reviews. Molecular cell biology · 2025Review
- Article
- Investigating the circadian rhythm signaling pathway in HTLV-1 pathogenesis using Boolean analysis.Virus research · 2025Article
- Identification of Potential Therapeutic Targets for Sensorineural Hearing Loss and Evaluation of Drug Development Potential Using Mendelian Randomization Analysis.Bioengineering (Basel, Switzerland) · 2025Article
- The hidden rhythms of epilepsy: exploring biological clocks and epileptic seizure dynamics.Acta epileptologica · 2025Review
- Microglial clock dysfunction during neuroinflammation impairs oligodendrocyte progenitor cell recruitment and disrupts neuroimmune homeostasis.Frontiers in immunology · 2025Article
- Chronotherapy and intervertebral disc degeneration: understanding the role of circadian rhythm in degenerative processes.Frontiers in cell and developmental biology · 2025Review
- Severe attenuation of circadian clock output in the heart following sustained augmentation of cardiomyocyte protein O-GlcNAcylation.Frontiers in cardiovascular medicine · 2025Article
- Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Timing Mechanisms for Circadian Seizures.Clocks & sleep · 2024Review
81 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DBP (albumin D-site-binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor) are the three members of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family. All three of these transcriptional regulatory proteins accumulate with robust circadian rhythms in tissues with high amplitudes of clock gene expression, such as the suprachiasmatic nucleus (SCN) and the liver. However, they are expressed at nearly invariable levels in most brain regions, in which clock gene expression only cycles with low amplitude. Here we show that mice deficient for all three PAR bZip proteins are highly susceptible to generalized spontaneous and audiogenic epilepsies that frequently are lethal. Transcriptome profiling revealed pyridoxal kinase (Pdxk) as a target gene of PAR bZip proteins in both liver and brain. Pyridoxal kinase converts vitamin B6 derivatives into pyridoxal phosphate (PLP), the coenzyme of many enzymes involved in amino acid and neurotransmitter metabolism. PAR bZip-deficient mice show decreased brain levels of PLP, serotonin, and dopamine, and such changes have previously been reported to cause epilepsies in other systems. Hence, the expression of some clock-controlled genes, such as Pdxk, may have to remain within narrow limits in the brain. This could explain why the circadian oscillator has evolved to generate only low-amplitude cycles in most brain regions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.