Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide maps of chromatin binding site for Mdm2.

ABSTRACT: The MDM2 oncoprotein is an essential component of the p53 pathway. Although MDM2 has been widely described as a major negative regulator of the p53 tumor suppressor, growing evidences support the notion that Mdm2 functions are also mediated through p53 independent mechanisms. We found that MDM2 is recruited on chromatin. By ChIP-Seq (using MDM2 antibody) of H1299 cells exhibiting MDM2 recruitment on chromatin, we identified at the whole genome level MDM2 binding sites. Both input and IPped-DNA were exhaustively sequenced and mapped on human genome

ORGANISM(S): Homo sapiens

PROVIDER: GSE64439 | GEO | 2016/06/09

SECONDARY ACCESSION(S): PRJNA271011

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [HCT116 microarray]

Project description:The Mdm2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that Mdm2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, Mdm2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the Mdm2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. Mdm2 physically associated with EZH2 on chromatin, enhancing the trimethylation of Histone 3 at lysine 27 and the ubiquitination of Histone 2A at lysine 119 (H2AK119) at its target genes. Removing Mdm2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, Mdm2 supports the Polycomb-mediated repression of lineage specific genes independent of p53. microarray analysis in HCT116 p53-/-cells

2015-12-31 | E-GEOD-73294 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [ChIP-Seq]

2015-12-31 | E-GEOD-73293 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [hMSC microarray]

2015-12-31 | E-GEOD-73601 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [RNA-Seq]

2015-12-31 | E-GEOD-73176 | biostudies-arrayexpress

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [HCT116 microarray]

2015-12-31 | GSE73294 | GEO

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [hMSC microarray]

2015-12-31 | GSE73601 | GEO

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [ChIP-Seq]

2015-12-31 | GSE73293 | GEO

Mdm2 enhances stemness-promoting chromatin modifications through the Polycomb Repressor Complex 2 in a p53-Independent Manner [RNA-Seq]

2015-12-31 | GSE73176 | GEO

Charting the impact of supraphysiologic MDM2 on gene regulatory circuits in sarcoma

Project description:Amplification of the ubiquitin ligase MDM2 is a common mechanism of P53 inactivation across human tumors. Here we investigated the impact of supraphysiologic MDM2 expression on chromatin topology, gene expression and cellular phenotypes in liposarcoma tumors and models. We identified three independent gene regulatory circuits that predominate in aggressive, dedifferentiated tumors. RUNX and AP-1 family transcription factors bind a shared set of enhancers associated with mesenchymal lineage genes that underlie the developmental state of these tumors. P53 and MDM2 co-occupy enhancers and promoters associated with P53 pathways. When highly expressed, MDM2 also binds an additional set of P53-independent promoters that engage in multi-way physical interactions and regulate genes involved in cell division, RNA splicing, translation and stress responses. We find that liposarcoma cells with low to moderate MDM2 levels are sensitive to P53 inhibitors and their combination with pro-apoptotic agents, but that cells with very high-level MDM2 amplification and expression resist treatment. Hence, heterogeneity of MDM2 expression between and within tumors may compromise therapeutic regimens. In conclusion, we distinguished P53-dependent and P53-independent circuits in MDM2 copy number amplified tumors whose interplay has implications for targeted therapy.

2023-04-10 | GSE213300 | GEO

MDM2 and MDM4 are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors

Project description:Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. We screened several MRT cell lines each with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers. We discovered MDM2 and MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Using two compounds currently in clinical development, idasanutlin and ATSP-7041, we show that MRT cells are more sensitive than other p53 wild-type cancer cell lines to MDM2 and dual MDM2/4 inhibition in vitro. These compounds cause significant upregulation of the p53 pathway in MRT cells, and sensitivity is ablated by CRISPR-Cas9-mediated inactivation of TP53. We show that loss of SMARCB1, a subunit of the SWI/SNF (BAF) complex mutated in nearly all MRT, sensitizes cells to MDM2 and MDM2/4 inhibition by enhancing p53-mediated apoptosis. Both MDM2 and MDM2/4 inhibition slowed MRT xenograft growth in vivo, with a five-day idasanutlin pulse causing marked regression of all xenografts including durable complete responses in 50% of mice. Together, these studies identify a genetic connection between mutations in the SWI/SNF chromatin-remodeling complex and the tumor suppressor gene p53, and provide preclinical evidence to support the targeting of MDM2 and MDM4 in this often-fatal pediatric cancer.

2019-02-04 | GSE124508 | 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