The clock gene BMAL1 inhibits macrophage motility, phagocytosis, and impairs defence against pneumonia
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ABSTRACT:
PROVIDER: PRJEB34772 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3581970_1.fastq.gz | Fastqsanger.gz | |||
| ERR3581970_2.fastq.gz | Fastqsanger.gz | |||
| ERR3581971_1.fastq.gz | Fastqsanger.gz | |||
| ERR3581971_2.fastq.gz | Fastqsanger.gz | |||
| ERR3581972_1.fastq.gz | Fastqsanger.gz |
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Project description:The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. RNAseq was performed on peritoneal macrophages from wild type and BMAL1 knock out mice.
2019-12-20 | E-MTAB-8411 | biostudies-arrayexpress
Project description:The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. Infected mice show both reduced weight loss and lower bacterial burden in circulating blood. In vivo studies of macrophage phagocytosis reveal increased bacterial ingestion following Bmal1 deletion, which was also seen in vitro. BMAL1-/- macrophages exhibited marked differences in actin cytoskeletal organization, a phosphoproteome enriched for cytoskeletal changes, with reduced phosphocofilin and increased active RhoA. Further analysis of the BMAL1-/- macrophages identified altered cell morphology and increased motility. Mechanistically, BMAL1 regulated a network of cell movement genes, 148 of which were within 100 kb of high-confidence BMAL1 binding sites. Links to RhoA function were identified, with 29 genes impacting RhoA expression or activation. RhoA inhibition restored the phagocytic phenotype to that seen in control macrophages. In summary, we identify a surprising gain of antibacterial function due to loss of BMAL1 in macrophages, associated with a RhoA-dependent cytoskeletal change, an increase in cell motility, and gain of phagocytic function.
| S-EPMC6983378 | biostudies-literature
Project description:The clock gene BMAL1 inhibits macrophage motility, phagocytosis, and impairs defence against pneumonia
2020-01-10 | E-MTAB-8411 | ExpressionAtlas
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:Organ development relies on interactions among different cell types that form three-dimensional structures to carry out specific tasks. This process often involves active migration of progenitor cells toward specific positions within the embryo, where the cells then become immotile and form stable connections among each other and with neighboring cell types. Yet, surprisingly little is known about processes of motility loss and the emerging organization of the cells at the site where the organ forms. In this work, we study these the process of motility loss processes using zebrafish primordial germ cells as an in vivo model. We show that changes in embryonic tissues as well as cell-autonomous events regulate germ cells’ behavior as they arrive at their target region. Importantly, we find that reduction in germ cell motility is correlated with the decay of RNA encoding for Dead end 1 (Dnd1), a conserved vertebrate RNA-binding protein that is essential for PGC migration. Indeed, decreasing or increasing the level of Dnd1 results in a premature or delayed stop to motility, respectively. These findings represent a novel RNA decay-based mechanism for timing the duration of cell migration in vivo.
2025-12-10 | GSE310575 | 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: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:We showed that Bmal1 mainly regulates clock gene initiation, with this functioning being highly conserved across species. compare RNA-seq and chip-seq between wildtype and mutant cells
2015-12-31 | E-GEOD-68416 | biostudies-arrayexpress
Project description:Genome profiling of BMAL1,TRIM28 and H3K9me3 analyzed by ChIP-seq in JM8+/+ and Bmal1-/- mESCs. Genome profiling of FlagBMAL1 in mESCs. High throughput capture chromosome conformation analysis (Hi-C) in JM8+/+ and Bmal1-/- mESCs. mRNA-seq analysis of JM8+/+ and Clock-/- mESCs
2025-08-14 | GSE263284 | GEO