Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene Model 129 (Gm129) Encodes a Novel Transcriptional Repressor that Modulates Circadian Gene Expression

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE53828 | GEO | 2014/01/07

SECONDARY ACCESSION(S): PRJNA233470

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptional Repressor Gm129 Modulates the Circadian Gene Expression by Inhibiting CLOCK:BMAL1 Activity

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

Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and delta-RRE Liver Transcriptomes

Project description:In mammals, the circadian clock consists of transcriptional and translational feedback loops through DNA cis-elements such as E-box and RRE. In this study, we established mutant mice deficient for rhythmic transcription of Bmal1 gene by deleting its upstream RRE elements. We observed apparently normal circadian rhythms in the mutant, but the circadian period and amplitude of the mutants were more susceptible to disturbance of CRY1 protein rhythm. Our findings demonstrate that the RRE-mediated feedback regulation of Bmal1 underpins the E-box-mediated rhythm in cooperation with CRY1-dependent posttranslational regulation of BMAL1 protein, thereby conferring the perturbation-resistant oscillation and chronologically organized output of the circadian clock.

2022-05-17 | GSE199061 | GEO

Differential expression of genes affected by CRY1 or CRY2 in the absence of PER and NR1D proteins

Project description:The transcription-translation feedback loop, the core clock mechanism, is required for circadian rhythm. CRY protein, including CRY1 and CRY2, plays an important repressor role in the regulation of clock genes. However, other proteins, like PER1, PER2, NR1D1 and NR1D2, in the loop mask the transcriptional effects of CRY. This study provides data to find candidate genes specifically affected by CRY1 or CRY2 in mouse embryonic fibroblast (MEF) cells.

2024-02-21 | GSE246853 | GEO

Interactome of the circadian clock protein PERIOD2 in human U2OS osteosarcoma cells after the resetting of the circadian clock

Project description:Circadian rhythms are a series of endogenous autonomous 24-hour oscillations generated by the circadian clock. At the molecular level, the circadian clock is generated by a transcription-translation feedback loop, where BMAL1 and CLOCK transcription factors of the positive arm activate the expression of CRYPTOCHROME and PERIOD (PER) genes of the negative arm as well as the circadian clock-regulated genes. In this project, we aimed at finding the interactome of PER2 protein in human U2OS osteosarcoma cell line using proximity-dependent biotin identification (BioID) technique. U2OS clones overexpressing PER2-BioID2 or BioID2 were treated with dexamethasone in order to reset the circadian rhythm, and cells were then incubated in biotin-containing media for 12 hours to label the proteins in close proximity of PER2-BioID2. Samples were collected after 36 and 48 hours of the resetting to identify the labeled proteins by mass spectrometry. In addition to known interactors such as CRY1 and CRY2, many novel interactors were identified. In summary, we obtained a network of PER2 interactome and confirmed some of the novel interactions using classical the co-immunoprecipitation method.

2022-04-22 | PXD025179 | Pride

ChIP-seq of three core components of the circadian clock (BMAL1, CLOCK and CRY1) in unsynchronized human U2OS cells

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

Circadian clock, carcinogenesis, chronochemotherapy connections

Project description:The circadian clock controls the expression of nearly 50% of protein coding genes in mice, and most likely in humans as well. Therefore, disruption of the circadian clock is presumed to have serious pathological effects including cancer. However, epidemiological studies on individuals with circadian disruption because of night shift or rotating shift work have produced contradictory data not conducive to scientific consensus as to whether circadian disruption increases the incidence of breast, ovarian, prostate or colorectal cancers. Similarly, genetically engineered mice with clock disruption do not exhibit spontaneous or radiation-induced cancers at higher incidence than wild-type controls. Because many cellular functions including the cell cycle and cell division are, at least in part, controlled by the molecular clock components (CLOCK, BMAL1, CRYs, PERs), it has also been expected that appropriate timing of chemotherapy may increase the efficacy of chemotherapeutic drugs and ameliorate their side effect. However, empirical attempts at chronochemotherapy have not produced beneficial outcomes. Using mice without and with human tumor xenografts, sites of DNA damage and repair following treatment with the anticancer drug cisplatin have been mapped genome-wide at single nucleotide resolution and as a function of circadian time. The data indicate that mechanism-based studies such as these may provide information necessary for devising rational chronochemotherapy regimens.

2021-06-22 | GSE178585 | GEO

Transcriptional Architecture and Chromatin Landscape of the Core Circadian Clock in Mammals [RNA-seq]

Project description:The mammalian circadian clock involves a transcriptional feedback loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases M-bM-^@M-^T a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Interestingly only 22% of mRNA cycling genes are driven by de novo transcription, suggesting that both transcriptional and post-transcriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling. Examination of whole transcriptome every 4hr during the circadian cycle in mouse liver

2012-08-31 | E-GEOD-39978 | biostudies-arrayexpress

Transcriptional Architecture and Chromatin Landscape of the Core Circadian Clock in Mammals [ChIP-seq]

Project description:The mammalian circadian clock involves a transcriptional feedback loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases - a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Interestingly only 22% of mRNA cycling genes are driven by de novo transcription, suggesting that both transcriptional and post-transcriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling. Examination of 9 transcriptional regulators, 2 RNAPII and 6 histone modifications every 4hr during the circadian cycle in mouse liver

2012-08-31 | E-GEOD-39977 | biostudies-arrayexpress

The circadian E3 ligase complex SCFFBXL3+CRY targets TLK2

Project description:We recently demonstrated that the circadian clock component CRY2 is an essential cofactor in the SCFFBXL3-mediated ubiquitination of c-MYC. Because our demonstration that CRY2 recruits phosphorylated substrates to SCFFBXL3 was unexpected, we investigated the scope of this role by searching for additional substrates of FBXL3 that require CRY1 or CRY2 as cofactors. Here, we describe an affinity purification mass spectrometry (APMS) screen through which we identified more than one hundred potential substrates of SCFFBXL3+CRY1/2, including the cell cycle regulated Tousled-like kinase, TLK2. Both CRY1 and CRY2 recruit TLK2 to SCFFBXL3, and TLK2 kinase activity is required for this interaction. Overexpression or genetic deletion of CRY1 and/or CRY2 decreases or enhances TLK2 protein abundance, respectively. These findings reinforce the idea that CRYs function as co-factors for SCFFBXL3, provide a resource of potential substrates, and establish a molecular connection between the circadian and cell cycle oscillators via CRY-modulated turnover of TLK2.

2019-11-12 | PXD009522 | Pride

Clock regulation of metabolites reveals coupling between transcription and metabolism

Project description:The circadian clock is intricately connected with metabolism, however the precise details of these connections are incomplete. Here we used high temporal resolution metabolite profiling to determine circadian regulation of mouse liver and cell autonomous metabolism. In mouse liver, we found ~50% of metabolites were circadian, with strong enrichment of the nucleotide, amino acid, and methylation pathways. In U2OS cells, 27% of metabolites were circadian, including amino acids and NAD biosynthesis, also clock controlled in liver. To assess whether cell autonomous metabolite rhythms were clock-dependent, we used RNAi to perturb Bmal1, Cry1, and Cry2. Bmal1 knockdown eliminated most metabolite rhythms, while Cry1 generally shortened and Cry2 lengthened rhythms. Surprisingly, we found Cry1 knockdown induced 8 hr rhythms in amino acid, methylation, and vitamin metabolites, decoupling metabolite and transcriptional rhythms. These results provide the first comprehensive views of circadian liver and cell autonomous metabolism.

2017-04-05 | MTBLS292 | MetaboLights

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data