Ontology highlight
ABSTRACT:
PROVIDER: PRJEB93884 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Although the molecular mechanism of the circadian clock is conserved across cells, its transcriptional outputs are highly tissue specific. To experimentally explore how the core CLOCK/BMAL1 heterodimer achieves this specificity, we investigated its protein interaction landscape at the chromatin by employing a method that combines chromatin immunoprecipitation with mass spectrometry-based quantitative proteomics (ChIP–MS). This approach yielded the first two-dimensional (temporal and tissue-specific) interaction map of CLOCK/BMAL1 at the chromatin and revealed a complex organ-dependent landscape of clock-associated protein interactions. Among these we identified three homeodomain containing transcription factors -PROX1, HFN1B and HOXA5- in liver, kidney and lung, respectively. Functional analyses demonstrated that these factors colocalize with CLOCK/BMAL1 at the chromatin physically interacting via their homeodomain and the BMAL1 C-terminal transactivation domain and act as transcriptional repressors. Deletion of these homeodomain factors in organ-derived cell lines led to upregulation of core clock genes and disrupted rhythmic transcription of tissue-specific targets. Our findings uncover a new class of tissue-specific circadian transcriptional repressors and suggest that the molecular clock does not solely impose a universal temporal program but is instead modulated by chromatin-bound cofactors—such as PROX1, HNF1B, and HOXA5—that shape tissue-specific transcriptional outputs
2026-06-29 | GSE302237 | GEO
Project description:Circadian gene expression in mammals relies on the oscillatory activity of the BMAL1/CLOCK transcription factor complex, rhythmically binds to DNA. Despite the conserved presence of BMAL1/CLOCK in all tissues, circadian transcriptional outputs minimally overlap between tissues. We therefore hypothesize that BMAL1/CLOCK interact with tissue and time-dependent regulators at the chromatin generating an environment that determines tissue-specific gene expression. To investigate this, we combined chromatin immunoprecipitation with mass spectrometry-based quantitative proteomics (ChIP-MS) to characterize chromatin-bound BMAL1/CLOCK protein complexes at the transcriptional active phase (ZT4, ZT7, ZT10), in mouse tissues (Liver, Kidney, Lung). Together we produced and analyzed 108 pulldowns using BMAL1 and CLOCK specific antibodies. This large scale study yield a two dimensional (time & space) interaction map identifying known and unknown BMAL1/CLOCK interacting core proteins consistently present and time & tissue-specific complex constituents.
2026-06-24 | PXD062751 | Pride
Project description:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK-BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK:BMAL1:CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized protein that directly interacts with BMAL1 and represses CLOCK:BMAL1 activity. In vitro and in vivo protein-DNA interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK:BMAL1 complex on DNA. Although Gm129-/- or Cry1-/- Gm129-/- mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit significant phase delay compared to control. Our results suggest that, in addition to CRYs and PERs, GM129 protein contributes to the transcriptional feedback loop by modulating CLOCK:BMAL1 activity as a transcriptional repressor. Examination of 3 transcriptional regulators in mouse liver
2014-01-07 | E-GEOD-53828 | biostudies-arrayexpress
Project description:Circadian gene expression in mammals relies on the oscillatory activity of the BMAL1/CLOCK transcription factor complex, rhythmically binds to DNA. Despite the conserved presence of BMAL1/CLOCK in all tissues, circadian transcriptional outputs minimally overlap between tissues. Revision for the project PXD062751
2026-06-24 | PXD077567 | Pride
Project description:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK-BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK:BMAL1:CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized protein that directly interacts with BMAL1 and represses CLOCK:BMAL1 activity. In vitro and in vivo protein-DNA interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK:BMAL1 complex on DNA. Although Gm129-/- or Cry1-/- Gm129-/- mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit significant phase delay compared to control. Our results suggest that, in addition to CRYs and PERs, GM129 protein contributes to the transcriptional feedback loop by modulating CLOCK:BMAL1 activity as a transcriptional repressor.
2014-01-07 | GSE53828 | GEO
Project description:Mammalian circadian rhythms are based on coupled transcriptional-translational feedback loops driven by the transcription factors CLOCK and BMAL1. Chromatin remodeling mechanisms are essential for the proper timing and extent of circadian gene expression. We report that the S-adenosylhomocysteine (SAH) hydrolysing enzyme AHCY binds to CLOCK-BMAL1 at chromatin and drives circadian transcription by promoting cyclic H3K4 trimethylation and recruitment of BMAL1 to chromatin.
2020-02-01 | GSE125720 | GEO
Project description:Mammalian circadian rhythms are based on coupled transcriptional-translational feedback loops driven by the transcription factors CLOCK and BMAL1. Chromatin remodeling mechanisms are essential for the proper timing and extent of circadian gene expression. We report that the S-adenosylhomocysteine (SAH) hydrolysing enzyme AHCY binds to CLOCK-BMAL1 at chromatin and drives circadian transcription by promoting cyclic H3K4 trimethylation and recruitment of BMAL1 to chromatin.
2021-01-11 | GSE126851 | GEO
Project description:Circadian rhythms in gene expression are coincident with 24hr dynamics in the recruitment of the core-clock transcription factor heterodimer CLOCK-BMAL1 to chromatin. In the liver, circadian chromatin is characterized by rhythmic histone modifications and the deposition of histone variant H2A.Z. However, other histone variants and the remodelers that work in conjunction with CLOCK-BMAL1 on variant chromatin remain poorly understood. Here, we reveal that H3.3 variant histone deposition peaks during the daytime in liver chromatin and that CLOCK-BMAL1 is recruited to H3.3 nucleosomes. Moreover, H3.3:CLOCK-BMAL1 associates with PBAF and BRG1/cBAF complexes - members of the SWI/SNF remodeler family - only during the active phase of the circadian cycle. In clock-disrupted Per1-/-; Per2-/- livers, we observe a depletion in ARID2, the central cog in the molecular assembly of the PBAF complex, accompanied by an increase in H3.3 incorporation. Remarkably, a disassembly of PBAF complex and the concurrent reduction in BRG1 triggers a remodeler reorganization in Per knockout livers, where BRM/cBAF now targets BMAL1 at readily-accessible genomic sites. An abundance of fragile acetylated H3.3 nucleosomes and a remodeler reorganization provide a mechanistic basis for BMAL1 activity in the absence of PER-mediated negative feedback.
2025-08-22 | PXD061974 | Pride
Project description:In mammals, circadian clocks are strictly suppressed during early embryonic stages as well as pluripotent stem cells, by the lack of CLOCK/BMAL1 mediated circadian feedback loops. During ontogenesis, the innate circadian clocks emerge gradually at a late developmental stage, then, with which the circadian temporal order is invested in each cell level throughout a body. Meanwhile, in the early developmental stage, a segmented body plan is essential for an intact developmental process and somitogenesis is controlled by another cell-autonomous oscillator, the segmentation clock, in the posterior presomitic mesoderm (PSM). In the present study, focusing upon the interaction between circadian key components and the segmentation clock, we investigated the effect of the CLOCK/BMAL1 on the segmentation clock Hes7 oscillation, revealing that the expression of functional CLOCK/BMAL1 severely interferes with the ultradian rhythm of segmentation clock in induced PSM and gastruloids. RNA sequencing analysis showed that the premature expression of CLOCK/BMAL1 affects the Hes7 transcription and its regulatory pathways. These results suggest that the suppression of CLOCK/BMAL1-mediated transcriptional regulation during the somitogenesis may be inevitable for intact mammalian development.
2021-12-09 | GSE181295 | GEO
Project description:To investigate the interaction between aging and microglial circadian rhythmicity, we examined mice deficient in the core clock transcription factor, BMAL1, in microglia.
2023-03-01 | GSE214514 | GEO