Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-sequencing and ChIP-sequencing in murine mesenchymal stem cells treated with Ezh2 inhibitor GSK126 or β-catenin siRNA

ABSTRACT: During mesenchymal stem cell (MSC) differentiation, both Wnt signaling and the development of a rigid cytoskeleton promote commitment to the osteoblastic over adipogenic lineage. β-catenin is thought to play a critical role in Wnt effects. We show that β-catenin was additive with cytoskeletal signals to prevent adipogenesis, and β-catenin knockdown promoted adipogenesis even when the actin cytoskeleton was depolymerized. β-catenin also prevented osteoblast commitment in a cytoskeletal-independent manner, with β-catenin knockdown enhancing lineage commitment. Chip-seq showed that β-catenin associated with the promoter of EZH2, a key component of the PRC2 complex that governs genome methylation. Knocking down β-catenin lowered EZH2 levels and H3K27me3 at osteogenic loci. Further, when EZH2 was inhibited, β-catenin ’s anti-differentiation effects were lost. These results indicate that regulating EZH2 activity is key to β-catenin effects on MSC to preserve MSC multipotentiality.

ORGANISM(S): Mus musculus

PROVIDER: GSE138980 | GEO | 2019/10/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

H3K27 Methyltransferase PRC2 Represses Wnt Genes to Facilitate Adipogenesis

Project description:The Wnt/b-catenin signaling inhibits adipogenesis. Genome-wide profiling studies have revealed the enrichment of histone H3K27 methyltransferase PRC2 on Wnt genes. However, the functional significance of such a direct link between the two types of developmental regulators in mammalian cells, and the role of PRC2 in adipogenesis, remain unclear. Here we show PRC2 and its H3K27 methyltransferase activity are required for adipogenesis. PRC2 directly represses Wnt1, 6, 10a and 10b genes in preadipocytes and during adipogenesis. Deletion of the enzymatic Ezh2 subunit of PRC2 eliminates H3K27me3 on Wnt promoters and de-represses Wnt expression, which leads to activation of Wnt/b-catenin signaling and inhibition of adipogenesis. Ectopic expression of the wild type Ezh2, but not the enzymatically inactive F667I mutant, prevents the loss of H3K27me3 and the defects in adipogenesis in Ezh2-/- preadipocytes. The adipogenesis defects in Ezh2-/- cells can be rescued by expression of adipogenic transcription factors PPARa, C/EBPb, or inhibitors of Wnt/b-catenin signaling. Interestingly, Ezh2-/- cells show marked increase of H3K27 acetylation globally as well as on Wnt promoters. These results indicate that H3K27 methyltransferase PRC2 directly represses Wnt genes to facilitate adipogenesis, and suggest that acetylation and trimethylation on H3K27 play opposing roles in regulating Wnt expression. To identify additional PRC2-regulated genes in preadipocytes, we performed microarray analysis in Ezh2flox/flox preadipocytes infected with retroviruses expressing Cre or vector alone.

2010-03-19 | E-GEOD-20054 | biostudies-arrayexpress

H3K27 Methyltransferase PRC2 Represses Wnt Genes to Facilitate Adipogenesis

2010-03-19 | GSE20054 | GEO

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [Cut & Run]

Project description:The lysine methyltransferase EZH2 is overexpressed in colorectal cancer (CRC) and has been found to be positively and negatively correlated with CRC patient survival depending on the study suggesting that EZH2 has a complex role in CRC. Here, we demonstrate that AKT-mediated EZH2 S21 phosphorylation induced EZH2 to trimethylate β-catenin at K49, which increased β-catenin’s binding to the chromatin. Additionally, EZH2-mediated β-catenin trimethylation induced β-catenin’s interaction with TCF1 and RNA polymerase II and resulted in a dramatic gain in genomic regions with β-catenin occupancy. Interestingly, EZH2 catalytic inhibition decreased stemness but increased migratory phenotypes of CRC cells with active AKT. Overall, we demonstrated that EZH2 modulates AKT-induced changes in gene expression through the AKT/EZH2/β-catenin axis in CRC. Our results suggest that EZH2 inhibitors have tumor-inhibiting and promoting effects in CRC as they inhibit EZH2-mediated methylation of histone and non-histone targets like β-catenin.

2023-08-23 | GSE226588 | GEO

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [ChIP-Seq]

2023-08-23 | GSE226587 | GEO

Activation of AKT induces EZH2-mediated β-catenin trimethylation in colorectal cancer. [RNA-Seq]

2023-08-23 | GSE226584 | GEO

β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma (DNA methylation array)

Project description:Adrenocortical carcinoma (ACC) is a rare cancer in which tissue-specific differentiation is paradoxically associated with dismal outcomes. The differentiated ACC subtype CIMP-high is prevalent, incurable, and routinely fatal. CIMP-high ACC possess abnormal DNA methylation and frequent β-catenin activating mutations. Here, we demonstrate that this differentiated state is maintained by a balance between nuclear, tissue-specific β-catenin-containing complexes and the ACC epigenome. On chromatin, β-catenin binds master adrenal transcription factor SF1 and hijacks the adrenocortical super-enhancer landscape to maintain differentiation. Off chromatin, β-catenin binds histone methyltransferase EZH2, which is redistributed by the CIMP-high DNA methylation signature. SF1/β-catenin and EZH2/β-catenin complexes exist in normal adrenals and are selected for through all phases of ACC evolution. EZH2 inhibition in CIMP-high ACC favors EZH2/β-catenin assembly and purges SF1/β-catenin from chromatin, erasing differentiation and restraining cancer growth in vitro and in vivo. Our studies illustrate how tissue-specific programs shape oncogene selection, surreptitiously encoding targetable therapeutic vulnerabilities.

2023-04-25 | GSE205272 | GEO

β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma (RNA-seq)

2023-04-25 | GSE205261 | GEO

β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma (ChIP-seq)

2023-04-25 | GSE205258 | GEO

β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma (ATAC-seq)

2023-04-25 | GSE205254 | GEO

CUT&RUN Sequencing of EZH2 binding sites in HEK293T cells expressing a Dual-specificity Aptamer that specifically increases O-GlcNAcylation on beta-catenin, when beta-catein was knocked-down

Project description:O-GlcNAc is a dynamic post-translational modification on thousands of intracellular proteins, it regulates protein functions and is involved in many metabolic diseases. Using a dual-specificity aptamer, we targeted the O-GlcNAc transferase (OGT) to endogenous β-catenin and specifically increased O-GlcNAcylation of β-catenin. We found that O-GlcNAc on β-catenin promoted its interaction with EZH2 regardless of the Wnt signaling status. To study how this interaction regulates the distribution of EZH2 on the genome, we performed Cleavage Under Targets and Release Using Nuclease (CUT&RUN) on HEK293T cells expressing individual (Ctrl.) or dual-specificity aptamers, under Wnt - and Wnt + conditions. This is a control experiment in beta-catenin knockdown cells.

2022-10-11 | GSE214775 | GEO

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