Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CRISPR Screen of Venetoclax Response-Associated Genes Identifies Transcription Factor ZNF740 as a Key Functional Regulator [RNA-Seq]

ABSTRACT: CRISPR Screen of Venetoclax Response-Associated Genes Identifies Transcription Factor ZNF740 as a Key Functional Regulator [RNA-Seq]

PROVIDER: PRJNA1111110 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR29012820_1.fastq.gz	Fastqsanger.gz
	SRR29012820_2.fastq.gz	Fastqsanger.gz
	SRR29012821_1.fastq.gz	Fastqsanger.gz
	SRR29012821_2.fastq.gz	Fastqsanger.gz
	SRR29012822_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 16

Similar Datasets

CRISPR Screen of Venetoclax Response-Associated Genes Identifies Transcription Factor ZNF740 as a Key Functional Regulator [CUT&Run]

Project description:BCL-2 inhibitors such as venetoclax offer therapeutic promise in acute myeloid leukemia (AML) and other cancers, but drug resistance poses a significant challenge. It is crucial to understand the mechanisms that regulate venetoclax response. While correlative studies have identified numerous genes linked to venetoclax sensitivity, their direct impact on the drug response remains unclear. In this study, we targeted around 1,400 genes upregulated in venetoclax-sensitive primary AML samples and carried out a CRISPR knockout screen to evaluate their direct effects on venetoclax response. Our screen identified the transcription factor ZNF740 as a critical regulator, with its expression consistently predicting venetoclax sensitivity across subtypes of the FAB classification. ZNF740 depletion leads to increased resistance to venetoclax, while its overexpression enhances sensitivity to the drug. Mechanistically, our integrative transcriptomic and genomic analysis identifies NOXA as a direct target of ZNF740, which negatively regulates MCL-1 protein stability. Loss of ZNF740 downregulates NOXA and increases the steady state protein levels of MCL-1 in AML cells. Restoring NOXA expression in ZNF740-depleted cells re-sensitizes AML cells to venetoclax treatment. Furthermore, we demonstrated that dual targeting of MCL-1 and BCL-2 effectively treats ZNF740-deficient AML in vivo. Together, our work systematically elucidates the causal relationship between venetoclax response signature genes and establishes ZNF740 as a novel transcription factor regulating venetoclax sensitivity.

2024-09-04 | GSE267343 | GEO

CRISPR Screen of Venetoclax Response-Associated Genes Identifies Transcription Factor ZNF740 as a Key Functional Regulator [RNA-Seq]

2024-09-04 | GSE267342 | GEO

CRISPR Screen of Venetoclax Response-Associated Genes Identifies Transcription Factor ZNF740 as a Key Functional Regulator [CUT&Run]

Project description:CRISPR Screen of Venetoclax Response-Associated Genes Identifies Transcription Factor ZNF740 as a Key Functional Regulator [CUT&Run]

| PRJNA1111109 | ENA

An In Vivo Genome-Wide CRISPR Screen Identifies the RNA-Binding Protein Staufen2 as a Key Regulator of Myeloid Leukemia

Project description:While Chronic Myelogenous Leukemia (CML) is generally well controlled with Imatinib and other kinase inhibitors, blast crisis CML (bcCML) continues to be resistant to current therapies and remains highly lethal. In this study, we identify the double stranded RNA binding protein Stau2 as a as key new dependency of bcCML. To define the impact of Staufen2 in myeloid leukemia, we developed a germline knockout with targeted loss of its RNA binding domains. Genetic deletion of Staufen2 led to a profound decrease in bcCML growth and propagation, and markedly improved overall survival in mouse models. Further, Staufen2 was also expressed and required for growth of primary bcCML as well as de novo AML patient samples, indicating a conserved utilization across human disease. Finally, an integrated computational analysis of eCLIP, RNA-Seq analysis and the functional genomic CRISPR screen identified Staufen2 as a regulator of a remarkable network of broad acting chromatin modifiers, resulting in changes in global histone methylation patterns.

2020-04-23 | GSE134971 | GEO

CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [CRISPR screen]

Project description:CRISPR-Cas screen in ILC2 identifies Mef2d as a regulator of GATA3 and type-2 immunity [CRISPR screen]

| PRJNA1090067 | ENA

An In Vivo Genome-Wide CRISPR Screen Identifies the RNA-Binding Protein Staufen2 as a Key Regulator of Myeloid Leukemia

Project description:An In Vivo Genome-Wide CRISPR Screen Identifies the RNA-Binding Protein Staufen2 as a Key Regulator of Myeloid Leukemia

| PRJNA556899 | ENA

Genome-wide CRISPR Screen Identifies DNTT as a Key Regulator of Inotuzumab Ozogamicin Response in B-cell Acute Lymphoblastic Leukemia

Project description:Genome-wide CRISPR Screen Identifies DNTT as a Key Regulator of Inotuzumab Ozogamicin Response in B-cell Acute Lymphoblastic Leukemia

| PRJNA1101988 | ENA

Genome wide CRISPR screen for Venetoclax resisatnce in MOLM13 cells using Brunello library

Project description:Genome wide CRISPR screen for Venetoclax resisatnce in MOLM13 cells using Brunello library

| PRJNA540212 | ENA

CRISPR screen identifies NUDT21 as a regulator of intron detention of the SAM synthetase MAT2A RNA

Project description:The only S-adenosymethionine (SAM) synthetase expressed in most human cells, MAT2A, is regulated by intron detention. Using a GFP fusion reporter, we conducted a CRISPR screen to identify regulators of this alternative splicing event. The screen identified METTL16, a known regulator of this process, and NUDT21. NUDT21 encodes the CFIm25 protein a member of the CFIm complex involved in alternative polyadenylation. Validation and follow-up studies support the idea that CFIm25 and the larger CFIm complex plays an unanticipated role in splicing of the MAT2A detained intron.

2021-05-04 | GSE172217 | GEO

Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation.

Project description:Despite decades of research, mechanisms controlling T cell activation remain only partially understood, which hampers T cell-based immune cancer therapies. Here, we performed a genome-wide CRISPR screen to search for genes that regulate T cell activation. Our screen confirmed many of the known regulators in proximal T cell receptor signaling and, importantly, also uncovered a previously uncharacterized regulator, FAM49B (family with sequence similarity 49 member B). FAM49B deficiency led to hyperactivation of Jurkat T cells following T cell receptor stimulation, as indicated by enhancement of CD69 induction, PAK phosphorylation, and actin assembly. FAM49B directly interacted with the active form of the small GTPase Rac, and genetic disruption of the FAM49B-Rac interaction compromised FAM49B function. Thus, FAM49B inhibits T cell activation by repressing Rac activity and modulating cytoskeleton reorganization.

| S-EPMC5924929 | biostudies-literature

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