Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

UHRF2 mediates resistance to DNA methylation reprogramming in primordial germ cells [RNAseq_PGCs]

ABSTRACT: In mammals, primordial germ cells (PGCs) undergo global erasure of DNA methylation with delayed demethylation of germline genes and selective retention of DNA methylation at young retrotransposons. However, the molecular mechanisms of persistent DNA methylation in PGCs remain unclear. Here we report that resistance to DNA methylation reprogramming in PGCs requires UHRF2, the paralog of the DNMT1 cofactor UHRF1. PGCs from Uhrf2 knock-out mice show loss of retrotransposon DNA methylation, while DNA methylation is unaffected in somatic cells of Uhrf2-/- mice. Furthermore, Uhrf2-deficient PGCs show precocious demethylation of germline genes and overexpress meiotic genes in females.

ORGANISM(S): Mus musculus

PROVIDER: GSE240967 | GEO | 2025/08/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

UHRF2 mediates resistance to DNA methylation reprogramming in primordial germ cells [RNAseq_E8.5]

Project description:In mammals, primordial germ cells (PGCs) undergo global erasure of DNA methylation with delayed demethylation of germline genes and selective retention of DNA methylation at young retrotransposons. However, the molecular mechanisms of persistent DNA methylation in PGCs remain unclear. Here we report that resistance to DNA methylation reprogramming in PGCs requires UHRF2, the paralog of the DNMT1 cofactor UHRF1. PGCs from Uhrf2 knock-out mice show loss of retrotransposon DNA methylation, while DNA methylation is unaffected in somatic cells of Uhrf2-/- mice. Furthermore, Uhrf2-deficient PGCs show precocious demethylation of germline genes and overexpress meiotic genes in females.

2025-08-12 | GSE240968 | GEO

UHRF2 mediates resistance to DNA methylation reprogramming in primordial germ cells [RRBS]

2025-08-12 | GSE240970 | GEO

Ubiquitome analysis of UHRF1 and UHRF2-deficient mESCs

Project description:The E3 ligase UHRF1 is an essential epigenetic cofactor for DNMT1 dependent maintenance DNA methylation, which provides a binding platform for DNMT1 by both cooperative binding of histones and hemi-methylated DNA as well as by ubiquitinating histone H3. Here, we conduct a comprehensive screen to identify novel ubiquitination targets of UHRF1 and its paralogue UHRF2 by comparing the ubiquitome of wildtype (wt), UHRF1- and UHRF2-deficient mouse embryonic stem cells. With an antibody-dependent enrichment of ubiquitin remnant motif-containing peptides followed by isobaric-labeling based quantitative mass spectrometry, we find both known and novel E3 ligase substrates of UHRF1 involved in a variety of biological processes such as RNA processing, DNA methylation and DNA damage repair.

2017-10-24 | PXD006593 | Pride

UHRF2 Commissions the Accomplishment of DNA Demethylation through Allosteric Activation by 5hmC and K33-linked Ubiquitination of XRCC1

Project description:The transition of oxidized 5-methylcytosine (5mC) intermediates into base excision repair (BER) pipeline to complete DNA demethylation remains enigmatic. We report here that UHRF2, the only paralog of UHRF1 in mammals that is neither able to maintain 5mC nor to rescue Uhrf1-/- phenotype, is physically and functionally associated with BER. UHRF2 is allosterically activated by 5-hydroxymethylcytosine (5hmC) and acts as a ubiquitin E3 ligase to catalyze K33-linked polyubiquitination of XRCC1, a core subunit of the BER complex. This nonproteolytic action stimulates the interaction of XRCC1 with the ubiquitin binding domain-bearing RAD23B, leading to the formation of the TDG-RAD23B-BER complex amenable to complete DNA demethylation. Integrative epigenomic analysis in mouse embryonic stem cells reveals that the Uhrf2-coordinated TDG-RAD23B-BER complex functionally links to the completion of DNA demethylation at promoters, and that during neuronal commitment, Uhrf2-associated and H3K4me1-marked latent enhancers undergo poised-to-active transition accompanied by H3K27ac acquisition. Accordingly, Uhrf2 ablation impairs DNA demethylation and abolishes neuronal differentiation. Together, these observations highlight the essentiality of 5hmC-switched UHRF2 E3 ligase activity in commissioning the accomplishment of active DNA demethylation.

2022-11-26 | GSE141297 | GEO

UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures [RNA-seq]

Project description:5-methylcytosine (5mC) regulates multiple cellular processes and is faithfully maintained following DNA replication. Ubiquitin-like PHD and ring finger domain-containing protein 1 (UHRF1) plays an important role in the maintenance of 5mC levels. Interestingly, UHRF1 has a paralog UHRF2 that has similar sequence and domain architecture, but the biological function of UHRF2 is not clear. Here, we have generated Uhrf2 knockout mice and characterized the role of UHRF2 in vivo. Uhrf2 knockout mice are viable, but the adult mice develop frequent spontaneous seizures and display abnormal electrical activities in brain. To explore possible mechanism beyond these phenomenon, we utilized high-throughput sequencing to identify global expression changes in Uhrf2 knockout mice brains. In addition, we explored genome-wide 5mc profiles in these samples to examine if UHRF2 regulates 5mc levels in specific genome loci.

2017-07-21 | GSE98360 | GEO

UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures [MeDIP-Seq, hMeDIP-Seq]

2017-07-21 | GSE98361 | GEO

Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice

2013-03-04 | GSE40412 | GEO

Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by Aid deficiency

Project description:Epigenetic reprogramming including demethylation of DNA occurs in mammalian primordial germ cells (PGCs) and in early embryos, and is important for the erasure of imprints and epimutations, and the return to pluripotency. The extent of this reprogramming and its molecular mechanisms are poorly understood. We previously showed that the cytidine deaminases Aid and Apobec1 can deaminate 5-methylcytosine in vitro and in E coli, and in the mouse are expressed in tissues in which demethylation occurs. Here we profiled DNA methylation throughout the genome by unbiased bisulfite Next Generation Sequencing (BS-Seq) in wildtype and Aid deficient PGCs at E13.5. Wildtype PGCs revealed dramatic genome-wide erasure of methylation to a level below that of methylation deficient (Np95-/-) ES cells, with female PGCs being less methylated than male ones. By contrast, Aid deficient PGCs were up to three times more methylated than wildtype ones; this substantial difference occurred throughout the genome, with introns, intergenic regions and transposons being relatively more methylated than exons. Relative hypermethylation in Aid deficient PGCs was confirmed by analysis of individual loci in the genome. Our results reveal that erasure of DNA methylation in the germ line is a global process, hence limiting the potential for transgenerational epigenetic inheritance. Aid deficiency interferes with genome-wide erasure of DNA methylation patterns, suggesting that Aid has a critical function in epigenetic reprogramming and potentially in restricting the inheritance of epimutations in mammals. Comparison of methylation in wild-type and Aid deficient mouse tissues

2010-01-26 | E-GEOD-19960 | biostudies-arrayexpress

Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice

Project description:Genome-wide DNA demethylation, including the erasure of genome imprints, in primordial germ cells (PGCs), is critical as a first step for creating the totipotent epigenome in the germ line. Here, we provide evidence that contrary to the prevailing model involving active DNA demethylation, imprint erasure in mouse PGCs occurs in a manner consistent with replication-coupled passive DNA demethylation: PGCs erase imprints during their rapid proliferation with little de novo as well as maintenance DNA methylation potential and no major chromatin alterations. Our findings necessitate the re-evaluation of and provide novel insights into the mechanism of genome-wide DNA demethylation in PGCs. We performed expression analysis of primordial germ cells (PGCs) at embryonic days 10.5-13.5. Because the number of PGCs available at these stages were low, cDNAs were amplified by the method that we previously published (Kurimoto et al. 2006, NAR 34: e42 (PMID 16547197)). To include analysis of PGC gene expression at E9.5, we re-normalized the data from our E9.5 PGC samples (GSM744103, GSM744104) from our previous publication (Hayashi et al., 2011, Cell 146: 519-32 (PMD 21820164)) together with the data from this submission.

2013-03-04 | E-GEOD-40412 | biostudies-arrayexpress

RNA-seq profiling of mouse PGC (Mus musculus)

Project description:PGCs undergo two distinct stages of demethylation before reaching a hypomethylated ground state at E13.5. Stage 1 occurs between E7.25- E9.5 in which PGCs experience a global loss of cytosine methylation. However, discreet loci escape this global loss of methylation and between E10.5-E13.5, stage 2 of demethylation takes place. In this stage these loci are targeted by Tet1 and Tet2 leading to the loss of the remaining methylation and resulting in the epigenetic ground state. Our data shows that Dnmt1 is responsible for maintaining the methylation of loci that escape stage 1 demethylation, and that it functions in a UHRF1 independent manner. Our data further demonstrates that when these loci lose methylation prior to stage 2 it results in early activation of the meiotic program, which leads to precocious differentiation of the germ line resulting in a decreased pool of PGCs in the embryo and subsequent infertility in adult mice.

2016-09-13 | GSE74938 | GEO

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