Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity

ABSTRACT: DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity

PROVIDER: PRJNA664200 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12664112_1.fastq.gz	Fastqsanger.gz
	SRR12664112_2.fastq.gz	Fastqsanger.gz
	SRR12664113_1.fastq.gz	Fastqsanger.gz
	SRR12664113_2.fastq.gz	Fastqsanger.gz
	SRR12664114_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 80

Similar Datasets

DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity (RNA-Seq)

Project description:DDB1 is typically recognized as a component of the Cullin4 (CUL4)-RING E3 ubiquitin ligase complex. Here, we show that DDB1 functions independently of CUL4 to promote adipogenesis and diet-induced obesity. In contrast to depletion of CUL4A or CUL4B that stimulates adipogenesis, lack of DDB1 dramatically suppresses the process. Re-introduction of a DDB1 mutant that lacks the binding ability to CUL4A or CUL4B fully restores adipogenesis in DDB1-deficient preadipocytes. Furthermore, while inducibly knocking out Cul4a or Cul4b in mice aggravates diet-induced obesity, Ddb1+/- mice are lean on high-fat diet. Mechanistically, by binding the bromodomain-containing histone reader BRWD3, DDB1 is recruited to acetylated histones in the proximal promoters of immediate-early response genes, where it facilitates the release of paused RNA polymerase II (Pol II) and activates the transcription of these genes. Our findings have thus uncovered a mechanism of activating the transcriptional cascade in adipogenesis by DDB1-mediated release of paused Pol II.

2023-09-17 | GSE158172 | GEO

DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity (ChIP-Seq)

2023-09-17 | GSE158171 | GEO

DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity (ChIP-seq II)

2023-09-17 | GSE168136 | GEO

DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity (ChIP-Seq)

Project description:DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity (ChIP-Seq)

| PRJNA664202 | ENA

DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity (RNA-Seq)

Project description:DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity (RNA-Seq)

| PRJNA664203 | ENA

DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity (ChIP-seq II)

Project description:DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity (ChIP-seq II)

| PRJNA706200 | ENA

DDB1 Binds Histone Reader BRWD3 to Activate the Transcriptional Cascade in Adipogenesis and Promote Onset of Obesity

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-17 | GSE158173 | GEO

BRWD3 promotes KDM5 degradation to maintain H3K4 methylation levels

Project description:Histone modifications are critical for regulating chromatin structure and gene expression. Dysregulation of histone modifications likely contributes to disease states and cancer. Depletion of the chromatin-binding protein BRWD3, a known substrate-specificity factor of the Cul4-DDB1 E3 ubiquitin ligase complex, results in increased in H3K4me1 levels. The underlying mechanism linking BRWD3 and H3K4 methylation, however, has yet to be defined. Here, we show that depleting BRWD3 not only causes an increase in H3K4me1 levels, but also causes a decrease in H3K4me3 levels, indicating that BRWD3 influences H3K4 methylation more broadly. Using immunoprecipitation coupled to quantitative mass spectrometry, we identified an interaction between BRWD3 and the H3K4-specific demethylase 5 (KDM5/Lid), an enzyme that removes tri- and di- methyl marks from H3K4. Moreover, analysis of ChIP-seq data revealed that BRWD3 and KDM5 are significantly co-localized throughout the genome and that sites of H3K4me3 are highly enriched at BRWD3 binding sites. We show that BRWD3 promotes K48-linked polyubiquitination and degradation of KDM5 and that KDM5 degradation is dependent on both BRWD3 and Cul4. Critically, depleting KDM5 fully restores altered H3K4me3 levels and partially restores H3K4me1 levels upon BRWD3 depletion. Together, our results demonstrate that BRWD3 regulates KDM5 activity to balance H3K4 methylation levels.

2024-09-30 | GSE236629 | GEO

BRWD3 targets KDM5/Lid for degradation to maintain H3K4 methylation levels

Project description:Histone modifications are critical for regulating chromatin structure and gene expression. Dysregulation of histone modification levels may contribute to disease development and cancer. Therefore, understanding histone modifications is essential for development and disease. The chromatin-binding protein BRWD3, a known substrate-specificity factor of the Cul4-DDB1 E3 ubiquitin ligase complex, is required for maintaining active histone modification levels. Loss of BRWD3 function causes an increase in H3K4me1 levels. The underline mechanism, however, is unknown. We found that BRWD3 depletion also causes a decrease in H3K4me3 levels. To reveal the mechanism by which BRWD3 regulates the H3K4 methylation levels, we performed BRWD3-IP mass-spectrometry. We identified an interaction between BRWD3 and the lysine-specific demethylase 5 (KDM5/Lid), an enzyme that removes tri- and di- methyl marks from lysine 4 on histone H3. Moreover, analysis of ChIP-seq data revealed that BRWD3 and KDM5 are significantly co-localized throughout the genome. We show that BRWD3 promotes K48-linked ubiquitination of KDM5. Consistent with this, KDM5/Lid is rapidly degraded in a proteasome-dependent manner with a half-life of less than 30 mins. Critically, KDM5/Lid degradation is dependent on both BRWD3 and Cul4. In addition, we have found that BRWD3 is suppressor of Position-effect variegation (PEV). Loss of a single copy of KDM5, however, partially rescues the the BRWD3 PEV phenotype. Our results suggest that BRWD3 targets KDM5/Lid for degradation to ensure the balance of H3K4me levels.

2023-09-19 | PXD039706 | Pride

Oval cells from DDB1 mutant mouse

Project description:Quiescent hepatic stem cells (HSCs) can be activated when hepatocyte proliferation is compromised. Chemical injury rodent models have been widely used to study the locazation, biomarkers, and signaling pathways in HSCs, but these models usually exhibit severe promiscuous toxicity and fail to distinguish damaged and non-damaged cells. Our goal is to establish new animal models to overcome these limitations, thereby providing new insights into HSC biology and application. We generated mutant mice with constitutive or inducible deletion of Damaged DNA Binding protein 1 (DDB1), an E3 ubiquitin ligase, in hepatocytes. We show that deletion of DDB1 abolishes self-renewal capacity of mouse hepatocytes in vivo, leading to compensatory activation and proliferation of DDB1-expressing OCs. Importantly, the DDB1 mutant mice exhibit very minor liver damage, compared to a chemical injury model. Microarray analysis reveals several previously unrecognized markers, enriched in oval cells. This genetic model in which irreversible inhibition of hepatocyte duplication results in HSC-driven liver regeneration. The DDB1 mutant mice can be broadly applied to studies of HSC differentiation, HSC niche and HSCs as origin of liver cancer. Total RNA obtained from isolated EpCAM+ cells from DDB1 mutant mice compared to wild type hepatocytes

2012-01-01 | E-GEOD-31588 | biostudies-arrayexpress

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