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Mutant IDH disables p53 tumor suppression [CUT&RUN]

ABSTRACT: Mutant IDH disables p53 tumor suppression [CUT&RUN]

PROVIDER: PRJNA1173479 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31011664_1.fastq.gz	Fastqsanger.gz
	SRR31011664_2.fastq.gz	Fastqsanger.gz
	SRR31011665_1.fastq.gz	Fastqsanger.gz
	SRR31011665_2.fastq.gz	Fastqsanger.gz
	SRR31011666_1.fastq.gz	Fastqsanger.gz

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Mutant IDH disables p53 tumor suppression [CUT&RUN]

Project description:p53 prevents tumor initiation and progression by adapting cell fate via transcriptional regulation of target gene networks. Here, we find that cancer associated mutations in isocitrate dehydrogenase (IDH) can uncouple p53 activity from tumor suppression by perturbing chromatin states that determine target gene expression. Mutant IDH impairs tumor regressions and promotes outgrowth of cancer cells with transcriptionally active, wild type p53 in a mouse model of liver cancer where restoration of p53 activity results in tumor clearance. Mutant IDH alters p53 target gene expression through the oncometabolite 2-hydroxyglutarate (2-HG), an inhibitor of alpha-ketoglutarate (KG) dependent chromatin remodeling enzymes, without preventing p53 accumulation or global genomic binding. Rather, mutant IDH alters chromatin accessibility landscapes that dictate target gene expression. Mutant IDH interferes with the expression of pro-apoptotic p53 targets, including the death ligand receptor Fas that enables p53 dependent liver tumor regressions. Pharmacological inhibition of mutant IDH in TP53 wildtype cholangiocarcinoma cells, a tumor type where p53 and IDH mutations are mutually exclusive, potentiates p53 target gene expression and sensitizes cells to Fas ligand and chemotherapy induced apoptosis. Therefore, we implicate disruption of p53 target gene regulation as a reversable, oncogenic feature of cancer associated IDH mutations.

2025-04-30 | GSE279555 | GEO

Mutant IDH disables p53 tumor suppression [RNA-seq]

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Mutant IDH disables p53 tumor suppression [RNA-seq]

Project description:Mutant IDH disables p53 tumor suppression [RNA-seq]

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Nucleosomes gate cofactor access to the transcription factor p53 [CUT&Run]

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CUT&RUN HUDEP1 OE SOX6-Flag

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2023-04-07 | E-MTAB-12800 | biostudies-arrayexpress

Identification of chromatin states during zebrafish gastrulation using CUT&RUN and CUT&Tag

Project description:Here we describe successful implementation of CUT&RUN for profiling protein-DNA interactions in zebrafish embryos. We apply modified a CUT&RUN method to generate high resolution maps of enrichment for H3K4me3, H3K27me3, H3K9me3, and RNA polymerase II during zebrafish gastrulation. Using this data, we identify a conserved subset of developmental genes that are enriched in both H3K4me3 and H3K27me3 during gastrulation, and we demonstrate the increased effectiveness of CUT&RUN for detecting protein enrichment at repetitive sequences with reduced mappability. Our work demonstrates the power of combining CUT&RUN with the strengths of the zebrafish system to better understand the changing embryonic chromatin landscape and its roles in shaping development.

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