RNA seq of liver homogenates collected every 4 hours for one 24 hour cycle from adipocyte knockouts for Bmal1
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE95357 | GEO | 2023/02/13
REPOSITORIES: GEO
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Project description:Circadian (~24 hour) clocks exist in almost all types of living organism and play a fundamental role in regulating daily physiological and behavioural processes. The transcription factor BMAL1 (ARNTL) is thought to be one of the principal drivers of the molecular clock in mammals since its deletion abolishes 24-hour activity patterning, an important physiological output of the clockwork. However, whether or not Bmal1-/- mice can nevertheless display molecular 24-hour rhythms is unknown. Here, we determined whether Bmal1 function is necessary for daily molecular oscillations in two tissues – skin fibroblasts and liver. Unexpectedly, both tissues exhibited robust 24-hour oscillations over 2-3 days in the absence of any exogenous synchronizers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. Indeed, molecular oscillations were pervasive throughout the transcriptome, proteome and phosphoproteome of Bmal1-/- mice. In particular, several proteins exhibited rhythmic phosphorylation in both Bmal1-proficient and -deficient cells, highlighting an unanticipated role for post-translational regulators in 24-hour rhythms in the absence of any known clock mechanisms.
2020-02-17 | PXD009243 | Pride
Project description:Circadian clocks exist in almost all levels of living organisms and play elementary roles in the persistence of regular physiological and behavioural processes. Canonical transcription/translation feedback loop models portray BMAL1 (ARNTL) as one of the principal drivers of circadian periodicity in mammalian systems. In this integrated multi-omics study, we demonstrate, for the first time, 24 hr circadian oscillations in the expression levels of several transcripts and proteins in dexamethasone-synchronized Bmal1-/- mouse fibroblast cells and liver tissue slices. Intriguingly, daily oscillations were also observed in phosphoproteome profiles in the absence of this core clock gene. Our findings reveal that Bmal1 knockout radically alters the expression and phosphorylation patterns of mice hepatic proteome, which possibly attributes to considerably different sets of rhythmic candidates compared to wild-type. It is, therefore, reasonable to accentuate that circadian rhythms are not obliterated in mammalian systems due to deletion of the core clock genes.
2020-02-14 | GSE111696 | GEO
Project description:Circadian clocks exist in almost all levels of living organisms and play elementary roles in the persistence of regular physiological and behavioural processes. Canonical transcription/translation feedback loop models portray BMAL1 (ARNTL) as one of the principal drivers of circadian periodicity in mammalian systems. In this integrated multi-omics study, we demonstrate, for the first time, 24 hr circadian oscillations in the expression levels of several transcripts and proteins in dexamethasone-synchronized Bmal1-/- mouse fibroblast cells and liver tissue slices. Intriguingly, daily oscillations were also observed in phosphoproteome profiles in the absence of this core clock gene. Our findings reveal that Bmal1 knockout radically alters the expression and phosphorylation patterns of mice hepatic proteome, which possibly attributes to considerably different sets of rhythmic candidates compared to wild-type. It is, therefore, reasonable to accentuate that circadian rhythms are not obliterated in mammalian systems due to deletion of the core clock genes.
2020-02-14 | GSE134333 | GEO
Project description:The mechanisms by which core clock components are spatially organized to ensure robust oscillations in mammals remains unclear. Here, we identify the positive limb factor BMAL1 as a phase-separating protein that forms dynamic biomolecular condensates essential for circadian transcription and behavior. Endogenous BMAL1 forms nuclear punctate that oscillate in sync with the circadian cycle. Deletion analysis and optogenetic clustering identify an N_x001E_-terminal 90-amino acid intrinsically disordered region whose phosphorylation state tunes BMAL1 phase separation. Besides, BMAL1 condensates behave as multi-molecular assemblies that selectively recruit CLOCK, P300, MED1, and are specifically promoted by E-box DNA. Functionally, an IDR-deleted BMAL1 mutant fails to rescue rhythmic transcription in Bmal1-KO cells and cannot restore locomotor rhythms when reintroduced into the SCN specific Bmal1‑KO mice. These findings establish BMAL1 condensates as dynamic transcriptional hubs that couple phase separation to circadian rhythm in cells and in vivo.
2026-03-31 | GSE325358 | GEO
Project description:The mechanisms by which core clock components are spatially organized to ensure robust oscillations in mammals remains unclear. Here, we identify the positive limb factor BMAL1 as a phase-separating protein that forms dynamic biomolecular condensates essential for circadian transcription and behavior. Endogenous BMAL1 forms nuclear punctate that oscillate in sync with the circadian cycle. Deletion analysis and optogenetic clustering identify an N_x001E_-terminal 90-amino acid intrinsically disordered region whose phosphorylation state tunes BMAL1 phase separation. Besides, BMAL1 condensates behave as multi-molecular assemblies that selectively recruit CLOCK, P300, MED1, and are specifically promoted by E-box DNA. Functionally, an IDR-deleted BMAL1 mutant fails to rescue rhythmic transcription in Bmal1-KO cells and cannot restore locomotor rhythms when reintroduced into the SCN specific Bmal1‑KO mice. These findings establish BMAL1 condensates as dynamic transcriptional hubs that couple phase separation to circadian rhythm in cells and in vivo.
2026-03-31 | GSE325862 | GEO
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:The circadian clock system regulates a wide range of physiological processes in mammals, and the core circadian clock gene Bmal1 is crucial for maintaining the oscillations of circadian clock system by controlling the rhythmic expression of numerous clock-controlled genes. These data offer a valuable resource for researchers studying the role of BMAL1 in liver physiology and pathology, as well as the broader field of circadian biology.
2024-12-23 | GSE284601 | GEO
Project description:The master transcription factor BMAL1-CLOCK is crucial for orchestrating rhythmic gene expression and governing circadian rhythms. Pharmacological manipulation of this central circadian regulator requires accessible protein cavities and selective compounds. By targeting BMAL1 through a resident cavity in its PAS-B domain, we demonstrate that the small-molecule Core Circadian Modulator (CCM) penetrates and substantially expands this pocket. Biochemical and cellular analyses validate CCM's target engagement selectivity, enabling direct access to BMAL1's transcriptional activities. CCM induces dose-dependent changes in PER2-Luc macrophage oscillations and selectively modifies expression patterns of circadian controlled genes. In activated macrophages, CCM modulates BMAL1-CLOCK controlled inflammatory and phagocytic pathways to promote their downregulation. Our findings demonstrate the feasibility of directly targeting BMAL1-CLOCK as a strategy for circadian regulation and targeting circadian-regulated processes
2025-02-03 | GSE255357 | GEO
Project description:While the circadian rhythm is a highly conserved phenomenon, it has highly specific functions, which differ from one cell type to another. Hence, although the master regulators BMAL1-CLOCK are conserved, the input and output conveying the tissue specificity vary. Through comparative analyses of ChIP-seq data in mouse liver and NIH3T3 fibroblasts, we reveal that only a fraction of BMAL1 binding sites are shared between different cell types and that many sites are bound, active and accessible in a cell-type-specific way. While we found a large fraction of the overall active liver transcriptome to be rhythmically expressed, rhythmic genes among BMAL1 targets are more enriched compared to the overall cyclic transcriptome in NIH3T3 than in liver. Thus, BMAL1 may launch and reinforce oscillations of a number of genes that propagate timing information rather than globally drive rhythmic gene expression.
2016-12-31 | GSE61775 | GEO
Project description:TMT analysis of proteomic changes in the gastrocnemius skeletal muscles of WT and Bmal1-KO mice, and Bmal1-KO mice rescued with AAV-mediated muscle-specific expression of Bmal1.
2024-10-03 | PXD054406 | Pride