Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MAT2A expression and methionine dependency in Diffuse Midline Gliomas creates a distinct metabolic and epi-genetic sensitivity

ABSTRACT: MAT2A expression and methionine dependency in Diffuse Midline Gliomas creates a distinct metabolic and epi-genetic sensitivity

PROVIDER: PRJNA671811 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12897900_1.fastq.gz	Fastqsanger.gz
	SRR12897900_2.fastq.gz	Fastqsanger.gz
	SRR12897901_1.fastq.gz	Fastqsanger.gz
	SRR12897901_2.fastq.gz	Fastqsanger.gz
	SRR12897902_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 42

Similar Datasets

MAT2A expression and methionine dependency in Diffuse Midline Gliomas creates a distinct metabolic and epi-genetic sensitivity

Project description:We generated a syngeneic H3K27M diffuse midline glioma (DMG) mouse model and performed total RNA seq on H3K27MPP cells and control cell lines H3wtMPP and Normal Neural stem cells. Aditionally we generate a Dox Inducible Mat2A Knockdown in that human DIPG cell line DIPG04 and performed RNA sequencing on cells treated with 2ug/ml Doxycyclin and no treatment

2022-01-28 | GSE160088 | GEO

MAT2A and methionine dependency are indispensible for H3K27M mutant gliomas.

Project description:Gliomas bearing driver mutations of histone 3 lysine 27 (H3K27M) are incurable brain tumors. H3K27M mutant tumors display unique epigenomes with global loss of the chromatin repressive H3K27 trimethylation mark. Here, we generated a syngeneic H3K27M mouse model to study the dependence upon amino acid (AA) metabolism by performing an AA drop out screen. H3K27M mutant cells, but not histone wildtype cells, were highly dependent on the amino acid, methionine. Interrogating the methionine cycle dependency through an siRNA screen identified the enzyme Methionine Adenosyltransferase 2A (MAT2A), which catalyzes production of S-adenosylmethionine (SAM), a methyl donor. Sensitivity to MAT2A loss in H3K27M mutant cells was not mediated through the canonical mechanism of MTAP deletion; instead, H3K27M mutant cells have lower MAT2A protein levels, which is mediated by Adenosylmethionine Decarboxylase 1 (AMD1) production of decarboxylated SAM (dcSAM). MAT2A loss induces global depletion of H3K36me3, a potent chromatin mark of transcriptional elongation, as evaluated by quantitative chromatin immunoprecipitation with reference exogenous genome sequencing (ChIP-Rx-Seq) in multiple DIPG lines. Tandem H3K36me3 ChIP-Rx-seq and RNA-seq identified several oncogenic and developmental transcriptional programs associated with MAT2A loss. Moreover, inducible knockdown of MAT2A or methionine-restricted diets (MR) extended survival in both syngeneic and patient-derived xenograft models (PDXs) in vivo. Collectively, our results provide novel connections between AA metabolism and the epigenome in H3K27M gliomas, suggesting that MAT2A, a central regulator of methionine metabolism, presents exploitable therapeutic vulnerabilities in H3K27M gliomas.

2022-01-28 | GSE160006 | GEO

MAT2A and methionine dependency are indispensible for H3K27M mutant gliomas.

Project description:MAT2A and methionine dependency are indispensible for H3K27M mutant gliomas.

| PRJNA671595 | ENA

Transcriptome analysis of methionine restriction or CRISPR knockout of AHCY or MAT2A in Rael cells

Project description:RNAseq was used to identify host and viral transcriptome changes in methionine restricted Rael cells or Rael cells expressing control, AHCY or MAT2A sgRNAs.

2022-07-11 | GSE190937 | GEO

MAT2A promotes reprogramming of the androgen response pathway in association with ERG and EZH2

Project description:To date there are very few tools to reverse the induced dedifferentiation program in CRPC and to improve the response to the androgen deprivation therapy. Here we report that MAT2A is an important oncogenic cofactor of ERG/EZH2 transcriptional reprogramming impacting significantly the androgenic pathway. Using RNA sequencing coupled with ATAC, here we reveal an important link between ERG/MAT2A and EZH2 that impact on AR signaling pathway. This aberrant epigenetic program can be reversed by MAT2A inhibition which establish a near physiologic AR transcriptional program. Targeting MAT2A alone or in combination with EZH2 inhibitors reverse stemness in multiple models including prostatospheres from human PDX and GEM models of aggressive prostate cancer. Targeting MAT2A enhance the sensitivity to the androgenic blockade by Enzalutamide and to EZH2 inhibitors

2023-07-15 | E-MTAB-12031 | biostudies-arrayexpress

MAT2A promotes reprogramming of the androgen response pathway in association with ERG and EZH2

2023-07-15 | E-MTAB-12029 | biostudies-arrayexpress

MAT2A promotes reprogramming of the androgen response pathway in association with ERG and EZH2

2023-08-07 | E-MTAB-12536 | biostudies-arrayexpress

MAT2A promotes reprogramming of the androgen response pathway in association with ERG and EZH2

2023-07-15 | E-MTAB-12025 | biostudies-arrayexpress

MAT2A inhibitor in cancer cell lines

Project description:MAT2A inhibitor is dosed to MTAP null cell lines, samples are collected for transcriptome profiling

2020-12-09 | GSE161706 | GEO

MAT2A promotes reprogramming of the androgen response pathway in association with ERG and EZH2 (ChIP-Seq)

2023-07-20 | E-MTAB-12990 | biostudies-arrayexpress