ArticlePLoS biology2011
Genome-wide and phase-specific DNA-binding rhythms of BMAL1 control circadian output functions in mouse liver.
Article in PLoS biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 307 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
307 citing papers in PubMed, 1 synthesis or guideline pooled it, 473 citations in OpenAlex.
- The cross-talk between leptin and circadian rhythm signaling proteins in physiological processes: a systematic review.Molecular biology reports · 2023Pooled it
- Circadian synchronization between diet and gut microbiota in modulating host's health.Gut microbes · 2026Review
- The club cell circadian clock regulates temporal patterns in leukocyte trafficking in chronic allergic airways disease.Mucosal immunology · 2026Article
- CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators.Nature cell biology · 2026Article
- D-Box Binding Protein (DBP) as a Circadian Output Regulator: Molecular Mechanisms, Tissue-Specific Functions, and Disease Relevance.International journal of molecular sciences · 2026Review
- Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period.eLife · 2026Article
- Deletion ofInternational journal of molecular sciences · 2026Article
- Multi-omic identification of key transcriptional regulatory programs during endurance exercise training in rats.Nature communications · 2026Article
- Interplay between circadian and other transcription factors-Implications for cycling transcriptome reprogramming.FEBS letters · 2026Review
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- Blood-spinal cord barrier disruption after spinal cord injury: a time-dependent mechanistic review.Frontiers in cellular neuroscience · 2026Review
- Maternal circadian disruption during pregnancy and offspring diabetic cardiovascular disease risk.Frontiers in cell and developmental biology · 2026Review
- Multilayer Timing of Cardiac Circadian Regulation Informs Prevention and Treatment of Cardiovascular Disease.Vascular health and risk management · 2026Article
- Mammalian synthetic gene circuits for biopharmaceutical development & manufacture.NPJ systems biology and applications · 2025Review
- The sleep-wake history contributes to rhythmic BMAL1 chromatin binding in the cerebral cortex but not in the liver.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A scheduler for rhythmic gene expression.Molecular systems biology · 2025Article
- Perturbation of the circadian clock in chronic diseases involving organ fibrosis.The Journal of clinical investigation · 2025Review
- Tandem association of CLOCK:BMAL1 complexes on DNA enables recruitment of CBP/p300 through multivalent interactions.bioRxiv : the preprint server for biology · 2025Article
- A scheduler for rhythmic gene expression.bioRxiv : the preprint server for biology · 2025Article
- Circadian clock model with sequestration repression motif: existence of periodic orbits and entrainment properties.Interface focus · 2025Article
247 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
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian circadian clock uses interlocked negative feedback loops in which the heterodimeric basic helix-loop-helix transcription factor BMAL1/CLOCK is a master regulator. While there is prominent control of liver functions by the circadian clock, the detailed links between circadian regulators and downstream targets are poorly known. Using chromatin immunoprecipitation combined with deep sequencing we obtained a time-resolved and genome-wide map of BMAL1 binding in mouse liver, which allowed us to identify over 2,000 binding sites, with peak binding narrowly centered around Zeitgeber time 6. Annotation of BMAL1 targets confirms carbohydrate and lipid metabolism as the major output of the circadian clock in mouse liver. Moreover, transcription regulators are largely overrepresented, several of which also exhibit circadian activity. Genes of the core circadian oscillator stand out as strongly bound, often at promoter and distal sites. Genomic sequence analysis of the sites identified E-boxes and tandem E1-E2 consensus elements. Electromobility shift assays showed that E1-E2 sites are bound by a dimer of BMAL1/CLOCK heterodimers with a spacing-dependent cooperative interaction, a finding that was further validated in transactivation assays. BMAL1 target genes showed cyclic mRNA expression profiles with a phase distribution centered at Zeitgeber time 10. Importantly, sites with E1-E2 elements showed tighter phases both in binding and mRNA accumulation. Finally, analyzing the temporal profiles of BMAL1 binding, precursor mRNA and mature mRNA levels showed how transcriptional and post-transcriptional regulation contribute differentially to circadian expression phase. Together, our analysis of a dynamic protein-DNA interactome uncovered how genes of the core circadian oscillator crosstalk and drive phase-specific circadian output programs in a complex tissue.
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.