Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An Adversarial DNA N6-methyladenine-Sensor Network Preserves Polycomb Silencing

ABSTRACT: Adenine N6 methylation in DNA (6mA) is widespread among bacteria and phage and is detected in mammalian genomes, where its function is largely unexplored. Here we show that 6mA deposition and removal are catalyzed, respectively, by the Mettl4 methyltransferase and Alkbh4 dioxygenase, and that 6mA accumulation in genic elements corresponds with transcriptional silencing. Inactivation of murine Mettl4 depletes 6mA and causes sublethality and craniofacial dysmorphism in incross progeny. We identify distinct 6mA sensor domains of prokaryotic origin within the MPND deubiquitinase and ASXL1, a component of the Polycomb repressive deubiquitinase (PR-DUB) complex, both of which act to remove monoubiquitin from histone H2A (H2A-K119Ub), a repressive mark. Deposition of 6mA by Mettl4 triggers the proteolytic destruction of both sensor proteins, thereby preserving H2A-K119Ub levels. Expression of the bacterial 6mA methyltransferase Dam, in contrast, fails to destroy either sensor. These findings uncover a native, adversarial 6mA network architecture that preserves Polycomb silencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE105006 | GEO | 2019/04/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Genome-wide maps of Usp16, ubH2A and gene expression profiles in wild type and Usp16 knock out mouse embryonic stem cells (ESCs) and embryoid bodies (EBs)

Project description:Polycomb Repressive Complex 1 and histone H2A ubiquitination (ubH2A) contribute to embryonic stem cell (ESC) pluripotency by repressing lineage-specific gene expression. However, whether active deubiquitination co-regulates ubH2A levels in ESCs and during differentiation is not known. Here, we report that the histone H2A deubiquitinase Usp16 regulates H2A deubiquitination and gene expression in ESCs, and importantly, is required for ESC differentiation. Usp16 knockout is embryonic lethal in mice, but does not affect ESC viability or identity. Usp16 binds to the promoter regions of a large number of genes in ESCs and Usp16 binding is inversely correlated with ubH2A levels and positively correlated with gene expression levels. Intriguingly, Usp16-/- ESCs fail to differentiate due to ubH2A-mediated repression of lineage-specific genes. Finally, Usp16, but not the enzymatically inactive mutant, rescues the differentiation defects of Usp16-/- ESCs. Therefore, this study identifies Usp16 and H2A deubiquitination as critical regulators of ESC gene expression and differentiation. Examination of binding pattern of H2A deubiquitinase Usp16 and ubH2A in mouse embryonic stem cells and embroid bodies

2014-05-02 | E-GEOD-52899 | biostudies-arrayexpress

RNA-seq of METTL4-mediated Nuclear N6-Deoxyadenosine Methylation Promotes Metastasis through Activating Multiple Metastasis-inducing targets

Project description:Understanding the gene profiling in METTL4/6mA/RP11-390F4.3 axis.

2022-11-21 | GSE171115 | GEO

ChIP-seq of METTL4-mediated Nuclear N6-Deoxyadenosine Methylation Promotes Metastasis through Activating Multiple Metastasis-inducing targets

Project description:Understanding the epigenome profiling of 6mA modification by METTL4, and HIF1 binding sites under hypoxia.

2022-11-21 | GSE171116 | GEO

Prevalent N6-methyldeoxyadenosine methylation in mammalian mitochondrial DNA

Project description:N6-methyldeoxyadenosine (6mA or m6dA), a well-known prokaryotic DNA modification has recently been shown to exist and play regulatory roles in eukaryotic genomic DNA. However, biological functions of 6mA in mammals remain to be explored largely due to its low abundance in most mammalian genomes. Here, we report a significant enrichment of 6mA in mammalian mitochondrial DNA (mtDNA), and identify METTL4 as a methyltransferase that installs 6mA. The level of 6mA in mtDNA is elevated up to over 0.02% of the total deoxyadenosines under hypoxia, representing ~7,00-fold enrichment over 6mA in the genomic DNA (gDNA) under normal growth conditions. The presence of 6mA negatively regulates mitochondrial transcription and balances mitochondrial function for cellular adaption to hypoxic stress. While DNA 5-methylcytosine (5mC) is a well-established, prevalent epigenetic mark in mammalian genomic DNA, our study reveals for the first time DNA 6mA methylation as a regulatory mark in mammalian mtDNA.

2020-03-24 | GSE102670 | GEO

Bap1 loss results in EZH2 dependent transformation

Project description:BAP1 and ASXL1 interact to form a polycomb deubiquitinase complex that removes monoubiquitin from histone H2A lysine 119 (H2AK119Ub). However, BAP1 and ASXL1 are mutated in distinct cancer types, consistent with independent roles in regulating epigenetic state and malignant transformation. Here we demonstrate that Bap1 loss results in increased trimethylated histone H3 lysine 27 (H3K27me3), elevated Ezh2 expression, and enhanced repression of Polycomb Repressive Complex 2 (PRC2) targets. These findings contrast with the reduction in H3K27me3 seen with Asxl1 loss. Conditional deletion of Bap1 and Ezh2 in vivo abrogates the myeloid progenitor expansion induced by Bap1 loss alone.

2015-10-05 | GSE61360 | GEO

Genome-wide maps of Usp16, ubH2A and gene expression profiles in wild type and Usp16 knock out mouse embryonic stem cells (ESCs) and embryoid bodies (EBs)

2014-05-02 | GSE52899 | GEO

Active N6-Methyladenine demethylation by DMAD regulates gene expression by modulating the binding dynamics of Polycomb protein in neurons

Project description:A Ten-Eleven Translocation (TET) ortholog has been identified as a DNA N6-Methyladenine (6mA) demethylase (DMAD) in Drosophila. However, the molecular roles of 6mA and DMAD remain largely unexplored. Through genome-wide 6mA and transcriptome profiling, we found that 6mA may serve as a repressive epigenetic mark on a group of genes involved in neurodevelopment and neuronal functions. Mechanistically, DMAD coordinates with Trithorax-related complex protein Wds to maintain active transcription by dynamically demethylating intragenic 6mA. Accumulation of 6mA by depleting DMAD recruits Polycomb protein Pc as 6mA reader and contributes to transcriptional repression. Our findings define an epigenetic role for 6mA and suggest that active 6mA demethylation by DMAD plays important roles in fly CNS function by coordinating additional epigenetic mechanisms.

2018-08-02 | GSE67855 | GEO

N6-Methyldeoxyadenosine Marks Active Transcription Start Sites in Chlamydomonas

Project description:N6-methyldeoxyadenosine (6mA or m6A) is a DNA modification preserved in prokaryotes to eukaryotes. It is widespread in bacteria, and functions in DNA mismatch repair, chromosome segregation, and virulence regulation. In contrast, the distribution and function of 6mA in eukaryotes have been unclear. Here we present a comprehensive analysis of the 6mA landscape in the genome of Chlamydomonas using new sequencing approaches. We identified the 6mA modification in 84% of genes in Chlamydomonas. We found that 6mA mainly locates at ApT dinucleotides around transcription start sites (TSS) with a bimodal distribution, and appears to mark active genes. A periodic pattern of 6mA deposition was also observed at base resolution, which is associated with nucleosome distribution near the TSS, suggesting a possible role in nucleosome positioning. The new genome-wide mapping of 6mA and its unique distribution in the Chlamydomonas genome suggest potential regulatory roles of 6mA in gene expression in eukaryotic organisms. Multiple sequencing methods are developed to profile the distribution of 6mA in Chlamydomonas including MeDIP-Seq, enzyme-treated DNA-Seq, MNase-Seq and RNA-Seq.

2015-04-30 | E-GEOD-62690 | biostudies-arrayexpress

RNA-seq analysis of peripheral nerve with conditional knockout of Bap1 deubiquitinase.

Project description:The goal of the experiment was to determine the role of H2A deubiquitinase in the nerve injury response in peripheral nerve. A Schwann cell specific knockout of the H2A deubiquitinase (Bap1) was generated to compare with wild type mice.

2022-05-02 | GSE197149 | GEO

Ubiquitinated histone H2A mapping in Drosophila ML-DmBG3 cells

Project description:Monoubiquitinated histone H2A produced by the Sce/Ring subunit of the Polycomb Repressive Complex 1 (PRC1) was mapped genome-wide in Drosophila ML-DmBG3 cells using chromatin immunoprecipitation followed by hybridization to Affymetrix tiling arrays. ML-DmBG3 chromatin immunoprecipitated with anti-histone H2AK119ub antibody and matching input chromatin were amplified, labeled and hybridized to Affymetrix tiling arrays to determine the locations of ubiquitinated H2A genome-wide.

2013-08-09 | E-GEOD-49634 | biostudies-arrayexpress

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