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Genome-wide identification of genes differentially expressed between control and Prdm14 overexpressing ES cells grown in serum conditions.

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Charles Bradshaw

PROVIDER: E-GEOD-45508 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-wide identification of genes differentially expressed between wild-type and Prdm14-deficient ES cells grown in 2i culture conditions.

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

Genome-wide identification of genes differentially expressed between control and Prdm14 overexpressing ES cells grown in serum conditions.

2013-04-01 | GSE45508 | GEO

Genome-wide identification of genes differentially expressed between wild-type and Prdm14-deficient ES cells grown in 2i culture conditions.

2013-04-01 | GSE45507 | GEO

Expression data from mouse wild type, PRDM14-overexpressing and Dnmts KO embryonic stem cells (ESCs).

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

Prdm14

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-04-01 | E-GEOD-45509 | biostudies-arrayexpress

Expresssion data of Prdm14 KO ESCs expressing each orthologues.

Project description:Gene regulatory networks underlying cellular pluripotency are controlled by a core circuitry of transcription factors, including POU5F1 and NANOG in mammals. However, the evolutionary origin and transformation of pluripotency transcriptional networks have not been elucidated in deuterostomes. PR domain-containing protein 14 (PRDM14) is specifically expressed in pluripotent cells and germ cells, and is required for establishing embryonic stem cells (ESCs) and primordial germ cells (PGCs) in mice. Here, we compared the functions and expression patterns of PRDM14 orthologues within deuterostomes. Amphioxus PRDM14, zebrafish PRDM14, and the combination of sea urchin PRDM14 and CBFA2T compensated for disruption of the mouse Prdm14 gene in terms of maintaining mouse ESC pluripotency. Interestingly, Prdm14 was expressed in motor neurons, but not in germ cells in amphioxus embryos as observed in zebrafish embryos. Therefore, our results suggest that the integration of the PRDM14–CBFA2T complex into the transcriptional network for pluripotency may be essential for stabilizing pluripotency during the early amniote development.

2019-01-29 | GSE112904 | GEO

PRDM14 Knockdown in human embryonic stem cells

Project description:To identify the gene changes after PRDM14 knockdown

2010-10-20 | GSE22795 | GEO

ETO Family Protein Mtgr1 Mediates Prdm14 Functions in Stem Cell Maintenance

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.

2016-01-01 | GSE74547 | GEO

Genome-wide mapping of PRDM14 binding sites in human embryonic stem cells

Project description:PRDM14 belongs to the PR (PRDI-BF1 and RIZ) domain proteins (PRDM) family which is a subclass of the SET domain proteins, a common domain found in histone modifying enzymes. PRDM14 has been previously implicated to regulate self-renewal of hESCs as knock-down of PRDM14 induced expression of differentiation marker genes and altered the cellular morphology. We showed that PRDM14 directly regulates the expression of key pluripotency gene POU5F1. Genome-wide location profiling experiments revealed that PRDM14 co-localized extensively with other key transcription factors such as OCT4, NANOG and SOX2. More importantly, in a gain-of-function assay, we showed that PRDM14 is able to enhance the efficiency of reprogramming of human fibroblasts in conjunction with OCT4, SOX2 and KLF4. Hence, PRDM14 exemplifies a key transcription factor that is required for the maintenance of human ESC identity and the reacquisition of pluripotency in human somatic cells.

2010-10-20 | GSE22767 | GEO

Expression data of PRDM14 overexpression in WT, Suz12 KO and Ctbp1/2 DKO ESCs

Project description:The pluripotency-associated transcriptional network is regulated by a core circuitry of transcription factors. The PR domain-containing protein, PRDM14, maintains pluripotency by activating and repressing transcription in a target gene-dependent manner. However, the mechanisms underlying dichotomic switching of PRDM14-mediated transcriptional control remains elusive. Here, we identified C-terminal binding protein 1/2 (CtBP1/2) as components of the PRDM14-mediated repressive complex. CtBP1/2 binding to PRDM14 depends on CBFA2T2, a core component of the PRDM14 complex. The loss of Ctbp1/2 impaired the PRDM14-mediated transcriptional repression required for pluripotency maintenance and primed to naïve pluripotency transition. Furthermore, CtBP1/2 also interacted with the PRC2 complexes, and the loss of Ctbp1/2 impaired the PRC2 and H3K27me3 enrichment at the target genes upon PRDM14 overexpression. These results suggest that evidence that the target gene-dependent transcriptional activity of PRDM14 is regulated by partner switching to ensure transition from primed to naïve pluripotency.

2020-07-15 | GSE134666 | GEO

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