Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Leukemia-associated ZMYND11-MBTD1 chimera induces leukemogenesis by hijacking TIP60 acetyltransferase and a PWWP-mediated chromatin association mechanism

ABSTRACT: Leukemia-associated ZMYND11-MBTD1 chimera induces leukemogenesis by hijacking TIP60 acetyltransferase and a PWWP-mediated chromatin association mechanism

PROVIDER: PRJNA632021 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11683752.fastq.gz	Fastqsanger.gz
	SRR11683753.fastq.gz	Fastqsanger.gz
	SRR11683754.fastq.gz	Fastqsanger.gz
	SRR11683755.fastq.gz	Fastqsanger.gz
	SRR11683756.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 29

Similar Datasets

Leukemia-associated ZMYND11-MBTD1 chimera induces leukemogenesis by hijacking TIP60 acetyltransferase and a PWWP-mediated chromatin association mechanism (RNA-seq)

Project description:The recurring t(10;17)(p15;q21) chromosomal translocation as detected in a subset of human acute myeloid leukemia (AML) patients produces an aberrant fusion gene ZMYND11-MBTD1 (ZM), the biological consequence of which, however, remains elusive. Here we show that ZM chimera confers primary murine hematopoietic stem/progenitor cells (HSPCs) an indefinite self-renewal capability ex vivo and causes AML in vivo. Genomics analyses revealed that ZM directly binds to and maintains high expression of pro-leukemic transcription factor (TF) genes such as Hox, Meis1, Myc, Myb, and Sox4. Mechanistically, ZM interacts with and recruits the Tip60 acetyltransferase complex, both of which occupy promoter-proximal genomic regions that are enriched with histone acetylation and devoid of H3K27me3. Furthermore, systematic mutagenesis of ZM revealed an essential requirement of Tip60 association and an H3K36me3-binding PWWP domain for leukemic transformation and proto-oncogene activation. Finally, inhibitor of histone acetylation-‘reading’ bromodomain proteins is efficacious in treating ZM-induced AML. Collectively, this study demonstrated the AML-causing effect of ZM chimera with relevant animal models, examined into its gene-regulatory functions and protein interactome, and reports a promising mechanism-based therapeutic strategy.

2021-01-14 | GSE150424 | GEO

Leukemia-associated ZMYND11-MBTD1 chimera induces leukemogenesis by hijacking TIP60 acetyltransferase and a PWWP-mediated chromatin association mechanism (ChIP-seq)

2021-01-14 | GSE149782 | GEO

ZMYND11-MBTD1 induces leukemogenesis through hijacking NuA4/TIP60 acetyltransferase complex and a PWWP-mediated chromatin association mechanism

Project description:Recurring chromosomal translocation t(10;17)(p15;q21) present in a subset of human acute myeloid leukemia (AML) patients creates an aberrant fusion gene termed ZMYND11-MBTD1 (ZM); however, its function remains undetermined. Here, we show that ZM confers primary murine hematopoietic stem/progenitor cells indefinite self-renewal capability ex vivo and causes AML in vivo. Genomics profilings reveal that ZM directly binds to and maintains high expression of pro-leukemic genes including Hoxa, Meis1, Myb, Myc and Sox4. Mechanistically, ZM recruits NuA4/Tip60 histone acetyltransferase complex to cis-regulatory elements, sustaining an active chromatin state enriched in histone acetylation and devoid of repressive histone marks. Systematic mutagenesis of ZM demonstrates essential requirements of Tip60 interaction and an H3K36me3-binding PWWP domain for oncogenesis. Inhibitor of histone acetylation-‘reading’ bromodomain proteins, which act downstream of ZM, is efficacious in treating ZM-induced AML. Collectively, this study demonstrates AML-causing effects of ZM, examines its gene-regulatory roles, and reports an attractive mechanism-guided therapeutic strategy.

2021-01-21 | PXD023702 | Pride

ZMYND11-MBTD1 induces leukemogenesis through hijacking NuA4/TIP60 acetyltransferase complex and a PWWP-mediated chromatin association mechanism

Project description:Recurring chromosomal translocation t(10;17)(p15;q21) present in a subset of human acute myeloid leukemia (AML) patients creates an aberrant fusion gene termed ZMYND11-MBTD1 (ZM); however, its function remains undetermined. Here, we show that ZM confers primary murine hematopoietic stem/progenitor cells indefinite self-renewal capability ex vivo and causes AML in vivo. Genomics profilings reveal that ZM directly binds to and maintains high expression of pro-leukemic genes including Hoxa, Meis1, Myb, c-Myc and Sox4. Mechanistically, ZM recruits NuA4/Tip60 histone acetyltransferase complex to cis-regulatory elements, sustaining an active chromatin state enriched in histone acetylation and devoid of repressive histone marks. Systematic mutagenesis of ZM demonstrates essential requirements of TIP60 interaction and an H3K36me3-binding PWWP domain for oncogenesis. Inhibitor of histone acetylation-‘reading’ bromodomain proteins, which act downstream of ZM, is efficacious in treating ZM-induced AML. Collectively, this study demonstrates AML-causing effects of ZM, examines its gene-regulatory roles, and reports an attractive mechanism-guided therapeutic strategy.

2021-01-14 | GSE161656 | GEO

Leukemia-associated ZMYND11-MBTD1 chimera induces leukemogenesis by hijacking TIP60 acetyltransferase and a PWWP-mediated chromatin association mechanism (ChIP-seq)

Project description:Leukemia-associated ZMYND11-MBTD1 chimera induces leukemogenesis by hijacking TIP60 acetyltransferase and a PWWP-mediated chromatin association mechanism (ChIP-seq)

| PRJNA630151 | ENA

Leukemia-associated ZMYND11-MBTD1 chimera induces leukemogenesis by hijacking TIP60 acetyltransferase and a PWWP-mediated chromatin association mechanism (RNA-seq)

Project description:Leukemia-associated ZMYND11-MBTD1 chimera induces leukemogenesis by hijacking TIP60 acetyltransferase and a PWWP-mediated chromatin association mechanism (RNA-seq)

| PRJNA632013 | ENA

Oncogenic ZMYND11-MBTD1 fusion protein anchors the NuA4/TIP60 histone acetyltransferase complex to the coding region of active genes

Project description:In this study, we characterize the fusion protein produced by the ZMYND11-MBTD1 translocation in acute myeloid leukemia. We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles ZMYND11 factor with the full acetyltransferase NuA4/TIP60 complex. The fusion protein leads to mislocalization NuA4/TIP60 complex in gene bodies, thereby increasing H4ac in specific gene targets. Finally, chromatin aberration is linked to aberrant gene expression and spliced isoforms.

2022-06-01 | GSE171673 | GEO

Oncogenic ZMYND11-MBTD1 fusion protein anchors the NuA4/TIP60 histone acetyltransferase complex to the coding region of active genes

Project description:A recurrent chromosomal translocation detected in cannibalistic acute myeloid leukemia leads to the production of a ZMYND11-MBTD1 fusion protein. - The ZMYND11-MBTD1 fusion protein is stably incorporated into the endogenous NuA4/TIP60 complex - ZMYND11-MBTD1 leads to mistargeting of NuA4-TIP60 activity to the coding region of ZMYND11-target genes, altering gene expression and transcript isoforms. - ZMYND11-MBTD1 binds the MYC gene leading to its upregulation, favoring growth and pluripotency while inhibiting differentiation markers.

2021-04-17 | MSV000087226 | MassIVE

ZMYND11-MBTD1 induces leukemogenesis through hijacking NuA4/TIP60 acetyltransferase complex and a PWWP-mediated chromatin association mechanism

Project description:ZMYND11-MBTD1 induces leukemogenesis through hijacking NuA4/TIP60 acetyltransferase complex and a PWWP-mediated chromatin association mechanism

| PRJNA679040 | ENA

ZMYND11-MBTD1 induces leukemogenesis through hijacking NuA4/TIP60 acetyltransferase complex and a PWWP-mediated chromatin association mechanism.

Project description:Recurring chromosomal translocation t(10;17)(p15;q21) present in a subset of human acute myeloid leukemia (AML) patients creates an aberrant fusion gene termed ZMYND11-MBTD1 (ZM); however, its function remains undetermined. Here, we show that ZM confers primary murine hematopoietic stem/progenitor cells indefinite self-renewal capability ex vivo and causes AML in vivo. Genomics profilings reveal that ZM directly binds to and maintains high expression of pro-leukemic genes including Hoxa, Meis1, Myb, Myc and Sox4. Mechanistically, ZM recruits the NuA4/Tip60 histone acetyltransferase complex to cis-regulatory elements, sustaining an active chromatin state enriched in histone acetylation and devoid of repressive histone marks. Systematic mutagenesis of ZM demonstrates essential requirements of Tip60 interaction and an H3K36me3-binding PWWP (Pro-Trp-Trp-Pro) domain for oncogenesis. Inhibitor of histone acetylation-'reading' bromodomain proteins, which act downstream of ZM, is efficacious in treating ZM-induced AML. Collectively, this study demonstrates AML-causing effects of ZM, examines its gene-regulatory roles, and reports an attractive mechanism-guided therapeutic strategy.

| S-EPMC7886901 | 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