Perturbation of the circadian clock contributes to radiotherapy-induced salivary gland hypofunction
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE234789 | GEO | 2024/01/01
REPOSITORIES: GEO
Similar Datasets
Project description:Ionizing radiation (IR) – induced salivary gland damage is a common adverse effect in radiotherapy for patients with head and neck cancers. Currently, there is no effective treatment for the resulting salivary gland hypofunction and xerostomia (dry mouth). Here we profiled the acute gene expression change in the mouse submandibular salivary gland, and defined its damage response patterns at the transcriptome level.
2021-09-23 | GSE184673 | GEO
Project description:Perturbation of the circadian clock contributes to radiotherapy-induced salivary gland hypofunction
| PRJNA983230 | ENA
Project description:The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. The circadian expressed and clock controlled genes represent about 10% of the transcripts in the mammalian cells, however the role of genome topology in the expression of genes in a circadian manner remains to be elucidated. In this study we investigated the characteristics and dynamics of the genomic loci that contact the clock controlled gene Dbp during the circadian cycle. To do so, we combined genome-wide interaction profiling by chromosome conformation capture-on-chip (4C) technology with analyses of circadian gene expression in synchronized mouse embryonic fibroblasts (MEFs). This approach allowed us to elucidate the three-dimensional organization of the genome during the circadian cycle around the clock controlled gene Dbp, paralleling its circadian expression. We found that the Dbp genomic environment remains largely similar during the circadian cycle. However, specific DNA regions change their frequency of interaction with Dbp as the circadian cycle progresses, delineating a Dbp circadian interactome. These specific changes are not present in Bmal1-/- MEF, suggesting that the clock machinery is implicated in shaping the genomic landscape around the Dbp locus. The Dbp interactome is enriched in DNA elements related to the clock system (E boxes). We found a spatial clustering of functionally related genes. The Dbp circadian interactome contains a subset of circadian genes whose expression closely parallels that for Dbp. Taken together, our results indicate that the Dbp subnuclear environment is organized to privilege the clock directed gene expression program.
2013-08-08 | GSE49582 | GEO
Project description:Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function. Keywords: time course
2009-10-22 | GSE17739 | 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 spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. The circadian expressed and clock controlled genes represent about 10% of the transcripts in the mammalian cells, however the role of genome topology in the expression of genes in a circadian manner remains to be elucidated. In this study we investigated the characteristics and dynamics of the genomic loci that contact the clock controlled gene Dbp during the circadian cycle. To do so, we combined genome-wide interaction profiling by chromosome conformation capture-on-chip (4C) technology with analyses of circadian gene expression in synchronized mouse embryonic fibroblasts (MEFs). This approach allowed us to elucidate the three-dimensional organization of the genome during the circadian cycle around the clock controlled gene Dbp, paralleling its circadian expression. We found that the Dbp genomic environment remains largely similar during the circadian cycle. However, specific DNA regions change their frequency of interaction with Dbp as the circadian cycle progresses, delineating a Dbp circadian interactome. These specific changes are not present in Bmal1-/- MEF, suggesting that the clock machinery is implicated in shaping the genomic landscape around the Dbp locus. The Dbp interactome is enriched in DNA elements related to the clock system (E boxes). We found a spatial clustering of functionally related genes. The Dbp circadian interactome contains a subset of circadian genes whose expression which closely parallel that for Dbp. Taken together, our results indicate that the Dbp subnuclear environment is organized to privilege the clock directed gene expression program. Wild type mouse embryonic fibroblasts at the circadian times (CT) 22, 26, 30, 34 and 46. Bmal1-/- mouse embrionic fibroblasts at CT 22 and CT 34 Biological replicate using an independent line of wild type mouse embrionic fibroblast at CT 22 and CT 34 This submission represents the chromosome conformation capture-on-chip component of the overall study
2013-08-08 | E-GEOD-49582 | biostudies-arrayexpress
Project description:Nuclear receptor subfamily 1 group D member 1 (NR1D1), also known as Rev-Erbα, is a circadian clock component that functions as a transcriptional repressor which coordinates circadian rhythm and cell metabolism. Altered circadian clock characteristics have been shown in malignant thyroid neoplasms, and NR1D1 is one of the recurrence-associated genes in papillary thyroid cancer. We aimed to investigate the biological role of NR1D1 in thyroid cancer cells.
2024-02-22 | GSE255015 | GEO
Project description:Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, M-oM-^AM-!ENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function. Experiment Overall Design: We examined the temporal profiles of gene expression in mouse distal nephron segments and collecting ducts. The RNA was extracted from microdissected distal convoluted tubules and connecting tubules (DCT/CNT samples) or, cortical collecting ducts (CCD samples). Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT M-bM-^@M-^S Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on two pools of RNA composed of equivalent amounts of RNA prepared from five animals at each ZT time-point.
2009-10-30 | E-GEOD-17739 | biostudies-arrayexpress
Project description:D-site binding protein, DBP, is a clock-controlled transcription factor and drives daily rhythms of physiological processes through the regulation of an array of genes harboring a DNA binding motif, D-box. DBP protein levels show a circadian oscillation with an extremely robust peak/trough ratio, but how the temporal pattern is regulated by post-translational regulation is unclear. In this study, we found that DBP protein levels are down-regulated by the ubiquitin-proteasome pathway. We screened 19 dominant-negative forms of E2 enzymes and found that UBE2G1 and UBE2T mediate the degradation of DBP. A proteomic analysis of DBP-interacting proteins and database screening identified Tumor necrosis factor Receptor-Associated Factor 7 (TRAF7), a RING-type E3 ligase, that forms a complex with UBE2G1 and/or UBE2T. Overexpression of TRAF7 down-regulated DBP protein level, while knockdown of TRAF7 up-regulated DBP in cultured cells. Knockout of TRAF7 in NIH3T3 cells revealed that TRAF7 mediates the time-of-the-day-dependent regulation of DBP levels. Furthermore, TRAF7 has a period-shortening effect on the cellular clock. Together, TRAF7 plays an important role in circadian clock oscillation through destabilization of DBP.
2024-08-28 | PXD051884 | 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