Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA153245 | ENA |
REPOSITORIES: ENA
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Project description:Germline cells reprogram extensive epigenetic modifications to ensure the cellular totipotency of the next generation and prevent accumulation of epimutations. Primordial germ cells (PGCs)1, the common source of both oocytes and sperm, erase genome-wide DNA methylation and histone H3 lysine 9 dimethylation (H3K9me2), a process called genome-wide epigenetic reprogramming2,3. However, little is known about the molecular mechanism of DNA demethylation by developing PGCs. Here we show that overexpression of PRDM14, a critical regulator for specification and early differentiation of PGCs, promotes global DNA demethylation in embryonic stem cells (ESCs). PRDM14 directly represses transcription of de novo DNA methyltransferase, Dnmt3b, but its repression is not sufficient for global DNA demethylation. Comparison of global gene expression profiles between PRDM14-overexpressing ESCs and Dnmts triple mutant ESCs clearly demonstrates that overexpression of PRDM14 activates about half of the genes silenced by DNA methylation in ESCs. Furthermore, PRDM14 directly interacts with TET1, which converts 5-methylcytosine to 5-hydroxymethylcytosine, and DNA demethylation by overexpression of PRDM14 is strongly disturbed by pharmacological inhibitors of the base excision repair (BER) pathway. We propose that formation of a PRDM14/TET1 complex triggers the activation of BER-dependent active demethylation across the whole genome of developing PGCs.
2021-02-17 | GSE36371 | GEO
Project description:Analysis of Prdm14 function in mouse embryonic stem cells. Prdm14 null and overexpressing ES cells were generated and analyzed by microarray, immunoflurescence, flow cytometry, ELISA, qPCR in different culture conditions. 2 samples (wild-type control and knockout) were analyzed in biological triplicates
2013-04-01 | E-GEOD-45507 | biostudies-arrayexpress
Project description:Analysis of Prdm14 function in mouse embryonic stem cells. Prdm14 null and overexpressing ES cells were generated and analyzed by microarray, immunoflurescence, flow cytometry, ELISA, qPCR in different culture conditions.
2013-04-01 | GSE45508 | GEO
Project description:Analysis of Prdm14 function in mouse embryonic stem cells. Prdm14 null and overexpressing ES cells were generated and analyzed by microarray, immunoflurescence, flow cytometry, ELISA, qPCR in different culture conditions.
2013-04-01 | GSE45507 | GEO
Project description:Purpose:The goals of this study is to analyze the gene expession pattern in mouse embryonic stem cells (ESCs) ovexpressed flag or mouse flag tagged Prdm14
2021-10-01 | GSE184802 | GEO
Project description:Prdm14 is a sequence-specific transcriptional regulator of embryonic stem cell (ESC) pluripotency and primordial germ cell (PGC) formation. It exerts its function, at least in part, through repressing genes associated with epigenetic modification and cell differentiation. Here, we show that this repressive function is mediated through an ETO-family co-repressor Mtgr1, which tightly binds to the pre-SET/SET domains of Prdm14 and co-occupies its genomic targets in mouse ESCs. Structure-guided point mutants abrogated the Prdm14-Mtgr1 association and disrupted Prdm14's function in mESC gene expression and PGC formation in vitro. Altogether, our work uncovers the molecular mechanism underlying Prdm14-mediated repression. Examination of Prdm14 and Mtgr1 occupancy by ChIP-seq and effects on gene expression in mouse embryonic stem cells
2016-07-03 | E-GEOD-74547 | biostudies-arrayexpress
Project description:Analysis of Prdm14 function in mouse embryonic stem cells. Prdm14 null and overexpressing ES cells were generated and analyzed by microarray, immunoflurescence, flow cytometry, ELISA, qPCR in different culture conditions. 2 samples (control and overexpression) were analyzed in biological triplicates
2013-04-01 | E-GEOD-45508 | biostudies-arrayexpress
Project description:Prdm14 is a PR-domain and zinc-finger protein whose expression is restricted to the pluripotent cells of an early embryo, embryonic stem cells (ESCs), and germ cells. Here we show that Prdm14 safeguards mouse ESC maintenance by preventing induction of extraembryonic endoderm (ExEn) fates. Conversely, Prdm14 overexpression impairs ExEn differentiation during embryoid body (EB) formation. Prdm14 occupies and represses genomic loci encoding ExEn differentiation factors, while also binding to and promoting expression of genes associated with ESC self-renewal. Prdm14-bound genomic regions significantly overlap those occupied by Nanog and Oct4, are enriched in a chromatin signature associated with distal regulatory elements, and contain a unique DNA-sequence motif recognized by Prdm14 in vitro. Our work identifies Prdm14 as a new member of mouse ESC (mESC) transcriptional network, which plays a dual role as a context-dependent transcriptional repressor or activator at distal silencers and enhancers. [ChIP-seq] Genome-wide mapping of Prdm14 binding sites in mouse embryonic stem cells: A FLAG-HA tagged Prdm14 (FH-Prdm14) mESC line was established. FLAG-HA double ChIP (ChIP with FLAG antibody followed by ChIP with HA antibody) was performed with FH-Prdm14 mESCs (Prdm14-ChIPseq) and as a negative control, wildtype mESCs (FLAG-HA_ChIPseq). H3K4me1 ChIPseq in mouse ES cells. Using published H3K4me1 data, we found there is a correlation between Prdm14 binding and H3K4me1 marks. So we obtained our own H3K4me1 data, using the wildtype mESCs. [RNA-seq] Global RNAseq analysis of Prdm14 knockdown in mouse embryonic stem cells: Analysis of poly(A)+ RNA from mESCs treated with non-targeting control siRNA and Prdm14 siRNA.
2010-12-23 | E-GEOD-25409 | biostudies-arrayexpress
Project description:The Nucleosome Remodeling and Deacetylase (NuRD) complex plays an important role in gene expression regulation, stem cell self-renewal, and lineage commitment. Yet little is known about the dynamics of NuRD during cellular differentiation. Here, we study these dynamics using genome-wide profiling and quantitative interaction proteomics in mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). The genomic targets of NuRD are highly dynamic during differentiation, with most binding occurring at cell-type specific promoters and enhancers. We identify ZFP296 as a novel, ESC-specific NuRD interactor that also interacts with the SIN3A complex. ChIP-sequencing in Zfp296 knockout (KO) ESCs reveals decreased NuRD binding both genome-wide and at ZFP296 binding sites, although this has little effect on the transcriptome. Nevertheless, Zfp296 KO ESCs exhibit delayed induction of lineage-specific markers upon differentiation to embryoid bodies. In summary, we identify an ESC-specific NuRD interacting protein which regulates genome-wide NuRD binding and cellular differentiation.
2018-10-11 | PXD010512 | Pride
Project description:Mouse embryonic stem cells (mESCs) fluctuate between a naïve inner cell mass (ICM)-like state and a primed epiblast-like state of pluripotency in serum, but are harnessed exclusively in a distinctive, apparently more naïve state of pluripotency (the ground state) with inhibitors for mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i). Understanding the mechanism ensuring a naïve state of pluripotency would be critical in realizing a full potential of ESCs. We show here that PRDM14, a PR domain-containing transcriptional regulator, ensures a naïve pluripotency by a dual mechanism: Antagonizing fibroblast growth factor receptor (FGFR) signaling that is activated paradoxically by the core transcriptional circuitry for pluripotency and directs a primed state and repressing de novo DNA methyltransferases that create a primed epiblast-like epigenome. PRDM14 exerts these functions by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression. Mouse Embryonic Stem Cells (mESCs) or mESC-like cells with different Prdm14 genotypes {Prdm14(+/+), Prdm14(-/-), and Prdm14(-/-) rescued with Avitag-EGFP-Prdm14 transgene [Prdm14(-/-)+AGP14]} are cultured on MEF in different medium [2i, Serum(day 2), Serum+MEK inhibitor (PD0325901) (day 2), Serum without LIF (day2)].
2013-01-18 | E-GEOD-42580 | biostudies-arrayexpress