The intestinal clock controls host’s metabolic response to diet by driving intestinal metabolic functions and the fiber-dependent microbiome
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE229963 | GEO | 2025/04/01
REPOSITORIES: GEO
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Project description:The human osteosarcoma cell line U2OS contains a functional circadian clock but expresses only a few rhythmic genes. We identified by ChIP-seq analysis 3040 binding sites of the circadian transcription factors BMAL1, CLOCK, and CRY1 in the genome of U2OS cells, comparable to the number found in highly rhythmic tissues like liver. ChIP was performed as described previously (Rey et al, 2011; doi:10.1371/journal.pbio.1000595) using confluent desynchronized U2OS cells and BMAL1, CLOCK, and CRY1-antibodies. Immunoprecipitated chromatin (10 ng DNA of 8 independent BMAL1 ChIPs with enrichment levels > 80-fold, 9 ng DNA of a CRY1 ChIP with 10-fold enrichment, and 8 ng DNA of a CLOCK ChIP with 40-fold enrichment) was used for library preparation. Three lanes of the BMAL1 library, and one lane each of the CRY1 and CLOCK library were sequenced on the Illumina Genome Analyzer IIx using Single-Read Cluster Generation Kit and 36 Cycle Sequencing Kit v2 (Lausanne Genomics Technologies Facility).
2016-02-11 | E-GEOD-44236 | biostudies-arrayexpress
Project description:The intestinal clock controls host’s metabolic response to diet by driving intestinal metabolic functions and the fiber-dependent microbiome
| PRJNA956901 | ENA
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:The human osteosarcoma cell line U2OS contains a functional circadian clock but expresses only a few rhythmic genes. We identified by ChIP-seq analysis 3040 binding sites of the circadian transcription factors BMAL1, CLOCK, and CRY1 in the genome of U2OS cells, comparable to the number found in highly rhythmic tissues like liver.
2016-02-11 | GSE44236 | GEO
Project description:Mammals rely on a network of circadian clocks to control daily systemic metabolism and physiology. The central pacemaker in the suprachiasmatic nucleus (SCN) is considered hierarchically dominant over peripheral clocks, whose degree of independence, or tissue-level autonomy, has never been ascertained in vivo. Using arrhythmic Bmal1-null mice, we generated animals with reconstituted circadian expression of BMAL1 exclusively in the liver (Liver-RE). High-throughput transcriptomics and metabolomics show that the liver has independent circadian functions specific for metabolic processes such as the NAD+ salvage pathway and glycogen turnover. However, although BMAL1 occupies chromatin at most genomic targets in Liver-RE mice, circadian expression is restricted to ∼10% of normally rhythmic transcripts. Finally, rhythmic clock gene expression is lost in Liver-RE mice under constant darkness. Hence, full circadian function in the liver depends on signals emanating from other clocks, and light contributes to tissue-autonomous clock function.
2019-06-13 | GSE132659 | GEO
Project description:The circadian clock in mammals temporally coordinates physiological and behavioural processes to anticipate daily rhythmic changes in their environment. Chronic disruption to circadian rhythms (e.g., through ageing or shift work) is thought to contribute to a multitude of diseases, including degeneration of the musculoskeletal system. The intervertebral disc (IVD) in the spine contains circadian clocks which control ~6% of the transcriptome in a rhythmic manner, including key genes involved in extracellular matrix (ECM) homeostasis. However, it remains largely unknown to what extent the local IVD molecular clock is required to drive rhythmic gene transcription and IVD physiology. In this work, we identified profound age-related changes of ECM microarchitecture and an endochondral ossification-like phenotype in the annulus fibrosus (AF) region of the IVD in the Col2a1-Bmal1 knockout mice. Reported here is the circadian time series RNA-Seq of the whole IVD in Bmal1 knockout mice.
2023-08-17 | E-MTAB-13083 | biostudies-arrayexpress
Project description:The goal of this study was to define the binding sites of the core circadian factors, BMAL1 and CLOCK across the genome in adult mouse skeletal muscle. We found that mitochondrial inner-membrane genes were among the most enriched rhythmic genes via gene ontology analysis, and ChIP-Seq analysis corroborated the role of Clock and Bmal1 in targeting promoters of mitochondrial inner-membrane genes.
2021-08-12 | GSE143334 | GEO
Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification. H2A.Z ChIP-Seq signal in the mouse liver over 6 time points of the 24h light:dark cycle, in wild-type and Bmal1-/- mice. Libraries containing a mononucleosome insert were sequenced using Ilumina HiSeq2000.
2014-01-06 | E-GEOD-47143 | biostudies-arrayexpress
Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification. Mouse liver nucleosome profile assayed by MNase-Seq over 6 time points of the 24h light:dark cycle (4 wild-type and 4 Bmal1-/- mice per time point). Illumina libraries containing a mononucleosome insert were sequenced using Ilumina HiSeq2000.
2014-01-06 | E-GEOD-47142 | biostudies-arrayexpress
Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification. Mouse liver CLK ChIP-Seq signal on Mnase-digested or sonicated chromatin, at 2 different time point (ZT22 and ZT06) from the same mice. Libraries were sequenced using Ilumina HiSeq2000. For Mnase-digested chromatin, libraries contained a mononucleosome insert (e.g., ~147bp), whereas the insert was ~150-300bp for sonicated chromatin.
2014-01-06 | E-GEOD-47144 | biostudies-arrayexpress