Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ZMYND8 co-localizes with NuRD on target genes and regulates recruitment of GATAD2A/NuRD to sites of DNA damage [ChIP-seq]

ABSTRACT: The NuRD complex is generally thought to repress transcription at both hyper- and hypomethylated regions in the genome. In addition, the complex is involved in the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The ZMYND8 MYND domain directly interacts with PPPL? motifs in the NuRD subunit GATAD2A. Furthermore, GATAD2A and GATAD2B exclusively form homodimers and they thus define mutually exclusive NuRD subcomplexes. ZMYND8 and MBD3 share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and expression of NuRD/ZMYND8 target genes in steady-state asynchronous cells. However, ZMYND8 facilitates immediate recruitment of GATAD2A/NuRD to induced sites of DNA damage. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to a distinct NuRD subcomplex.

ORGANISM(S): Homo sapiens

PROVIDER: GSE79834 | GEO | 2016/10/08

SECONDARY ACCESSION(S): PRJNA317161

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

ZMYND8 co-localizes with NuRD on target genes and regulates recruitment of GATAD2A/NuRD to sites of DNA damage [RNA-seq]

Project description:The NuRD complex is generally thought to repress transcription at both hyper- and hypomethylated regions in the genome. In addition, the complex is involved in the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The ZMYND8 MYND domain directly interacts with PPPL? motifs in the NuRD subunit GATAD2A. Furthermore, GATAD2A and GATAD2B exclusively form homodimers and they thus define mutually exclusive NuRD subcomplexes. ZMYND8 and MBD3 share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and expression of NuRD/ZMYND8 target genes in steady-state asynchronous cells. However, ZMYND8 facilitates immediate recruitment of GATAD2A/NuRD to induced sites of DNA damage. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to a distinct NuRD subcomplex.

2016-10-08 | GSE79835 | GEO

¬¬ZMYND8 co-localizes with NuRD on target genes and regulates poly-ADP-ribose dependent recruitment of GATAD2A/NuRD to sites of DNA damage

Project description:The NuRD complex is generally thought to repress transcription at both hyper- and hypomethylated regions in the genome. In addition, the complex is involved in the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The ZMYND8 MYND domain directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A. Furthermore, GATAD2A and GATAD2B exclusively form homodimers and they thus define mutually exclusive NuRD subcomplexes. ZMYND8 and MBD3 share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and expression of NuRD/ZMYND8 target genes in steady-state asynchronous cells. However, ZMYND8 facilitates immediate recruitment of GATAD2A/NuRD to induced sites of DNA damage in a PAR-dependent manner. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to a distinct NuRD subcomplex.

2016-10-10 | PXD003856 | Pride

ZMYND8 co-localizes with NuRD on target genes and regulates recruitment of GATAD2A/NuRD to sites of DNA damage

Project description:ZMYND8 co-localizes with NuRD on target genes and regulates recruitment of GATAD2A/NuRD to sites of DNA damage

| PRJNA317159 | ENA

GATAD2B containing NuRD complex drives R-loop dependent chromatin boundary formation at double strand breaks

Project description:To understand how components of NuRD could be recruited to DNA double-stranded break sites, we generate site-specific DNA double strand breaks through an inducible endonuclease AsiSI-ER system by adding 4-OHT, we applied antibodies against GATAD2B and HDAC1, both of which are components of NuRD complex, to pero ChIP in either DMSO or 4OHT treatment condition.

2024-04-17 | GSE230710 | GEO

Zinc Finger MYND-Type Containing 8 (ZMYND8) is epigenetically regulated in mutant Isocitrate Dehydrogenase 1 (IDH1) glioma to promote radioresistance [ChIP-seq]

Project description:Mutant isocitrate dehydrogenase 1 (mIDH1) alters the epigenetic regulation of chromatin, leading to a hypermethylation phenotype in adult glioma. This work focuses on identifying gene targets epigenetically dysregulated by mIDH1 to confer therapeutic resistance to ionizing radiation (IR). We evaluated changes in the transcriptome and epigenome in a radioresistant mIDH1 patient-derived glioma cell culture (GCC) following treatment with an mIDH1 specific inhibitor AGI-5198. We identified Zinc Finger MYND-Type Containing 8 (ZMYND8) as potential target of mIDH1 reprogramming. We suppressed ZMYND8 expression by shRNA knockdown and genetic knockout (KO) in mIDH1 glioma cells then assessed cellular viability to IR. We assessed the sensitivity of mIDH1 GCCS to pharmacological inhibition of ZMYND8-interacting partners: HDAC, BRD4, and PARP. Inhibition of mIDH1 lead to an upregulation of gene networks involved in replication stress. We found that the expression of ZMYND8, a regulator of DNA damage response was decreased in three patient-derived mIDH1 GCCs after treatment with AGI-5198. Knockdown of ZMYND8 expression sensitized mIDH1 GCCs to radiotherapy marked by decreased cellular viability. Following IR, mIDH1 glioma cells with ZMYND8 knockout (KO) exhibit significant phosphorylation of ATM and sustained γH2AX activation. ZMYND8 KO mIDH1 GCCs were further responsive to IR when treated with either BRD4 or HDAC inhibitors. PARP inhibition further enhanced the efficacy of radiotherapy in ZMYND8 KO mIDH1 glioma cells. These findings indicate the impact of ZMYND8 in the maintenance of genomic integrity and repair of IR-induced DNA damage in mIDH1 glioma.

2022-12-19 | GSE220715 | GEO

Zinc Finger MYND-Type Containing 8 (ZMYND8) is epigenetically regulated in mutant Isocitrate Dehydrogenase 1 (IDH1) glioma to promote radioresistance [RNA-seq]

2022-12-19 | GSE220716 | GEO

ZMYND8 co-localizes with NuRD on target genes and regulates recruitment of GATAD2A/NuRD to sites of DNA damage

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-10-08 | GSE79836 | GEO

Unique Protein Interaction Networks Define The Chromatin Remodeling Module of The NuRD Complex

Project description:The combination of four proteins and their paralogues including MBD2/3, GATAD2A/B, CDK2AP1, and CHD3/4/5, which we refer to as the MGCC module, form the chromatin remodeling module of the Nucleosome Remodeling and Deacetylase (NuRD) complex. To date, mechanisms by which the MGCC module acquires paralogue-specific function and specificity have not been addressed. Understanding the protein-protein interaction (PPI) network of the MGCC subunits is essential in defining underlying mechanisms of gene regulation. Therefore, using pulldown followed by mass spectrometry analysis (PD-MS) we report a proteome-wide interaction network of the MGCC module in a paralogue-specific manner. Our data also demonstrate that the disordered C-terminal region of CHD3/4/5 is a gateway to incorporate remodeling activity into both the ChAHP (CHD4, ADNP, HP1γ) and NuRD complexes in a mutually exclusive manner. We define a short aggregation prone region (APR) within the C-terminal segment of GATAD2B that is essential for the interaction of CHD4 and CDK2AP1 with the NuRD complex. Finally, we also report an association of CDK2AP1 with the Nuclear Receptor Co-Repressor (NCOR) complex. Overall, this study provides insight into the possible mechanisms through which the MGCC module can achieve specificity and diverse biological functions.

2023-03-11 | PXD025263 | Pride

Promoter Decommissioning by the NuRD Chromatin Remodeling Complex Triggers Synaptic Connectivity in the Mammalian Brain

Project description:Precise control of gene expression plays fundamental roles in brain development, but the roles of chromatin regulators in neuronal connectivity have remained poorly understood. Here, we find that depletion of the nucleosome remodeling and deacetylation (NuRD) complex in the cerebellar cortex by in vivo RNAi in rats and conditional knockout of the core NuRD subunit Chd4 in mice profoundly impairs the establishment of granule neuron parallel fiber/Purkinje cell synapses. In RNA-Seq analyses of Chd4 conditional knockout mice, we identify a set of nearly 200 genes that are repressed by the NuRD complex in the cerebellum in vivo. Genome-wide ChIP-Seq analyses reveal that the NuRD complex selectively decommissions the promoters of NuRD-repressed genes in the cerebellum in vivo by inducing the deacetylation of histone H3K9/14 and H3K27 and demethylation of H3K4 at these genes. Importantly, temporal control of promoter decommissioning and repression of NuRD target genes upon maturation of the cerebellum requires the NuRD complex. Finally, in a targeted in vivo RNAi screen of NuRD-repressed target genes, we identify the transcription factor Nhlh1, the RNA-binding protein Elavl2, and the presynaptic regulator Cplx3 as negative regulators of presynaptic differentiation in the cerebellar cortex. Together, these findings define NuRD-dependent promoter decommissioning as a developmentally regulated programming mechanism that releases the brake on presynaptic differentiation and thereby drives synaptic connectivity in the mammalian brain. Three distinct histone modifications using postnatal day 6 or day 22 cerebella from wild type (WT) or Chd4 conditional knockout (cKO) mice were examined in duplicate using libraries prepared with the Illumina ChIP-Seq DNA Sample Prep Kit and sequenced on the Illumina HiSeq 2000 platform.

2014-08-18 | E-GEOD-57758 | biostudies-arrayexpress

An ES cell–specific NuRD complex functions through interaction with Wdr5

Project description:The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit Mbd3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three Mbd3 isoforms (Mbd3a, Mbd3b, and Mbd3c) are expressed in mouse. Here, we find that the Mbd3c isoform contains a unique 50–amino acid N-terminal region that is necessary for Mbd3c to specifically interact with the histone H3 binding protein Wdr5. Domain analyses of Wdr5 reveal that the Wdr5 H3K4/MLL binding pocket is required for interaction with Mbd3c. We find that while Mbd3c KO ESCs differentiate normally, Mbd3c is redundant with the Mbd3a and Mbd3b isoforms in regulation of gene expression and ESC pluripotency, with the unique Mbd3c N-terminus required for this redundancy. Together, our data characterize a novel NuRD complex variant that functions specifically in ESCs

2017-04-27 | GSE80708 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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