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A Nuclear Receptor Coactivator is Essential for Esrrb Activity and the Induction and Maintenance of the ES Cell State

ABSTRACT: Orphan nuclear receptor Esrrb is vital in maintaining ES cells and like Oct4, Sox2 and Nanog is essential for self-renewal and pluripotency. Esrrb functions in somatic cells via LBD/AF-2-dependent coactivator recruitment to target genes. Here we show that in ES cells coactivator recruitment is similarly required and identify Ncoa3 as the Esrrb coactivator needed for activation of its target genes. Ncoa3 is essential for self-renewal and the induction of pluripotency in reprogramming, and genome-wide analysis of Ncoa3 binding reveals extensive overlap with Esrrb and pluripotency factors along with marks of active genes. Mechanistically, we show Ncoa3 is specifically required to bridge RNApol2 to Esrrb. We thus identify a new member of the ES pluripotency network and describe Esrrb and Ncoa3 as key factors linking core pluripotency factors to the general transcription machinery.

ORGANISM(S): Mus musculus

PROVIDER: GSE37262 | GEO | 2012/10/02

SECONDARY ACCESSION(S): PRJNA159151

REPOSITORIES: GEO

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A Nuclear Receptor Coactivator is Essential for Esrrb Activity and the Induction and Maintenance of the ES Cell State

Project description:Orphan nuclear receptor Esrrb is vital in maintaining ES cells and like Oct4, Sox2 and Nanog is essential for self-renewal and pluripotency. Esrrb functions in somatic cells via LBD/AF-2-dependent coactivator recruitment to target genes. Here we show that in ES cells coactivator recruitment is similarly required and identify Ncoa3 as the Esrrb coactivator needed for activation of its target genes. Ncoa3 is essential for self-renewal and the induction of pluripotency in reprogramming, and genome-wide analysis of Ncoa3 binding reveals extensive overlap with Esrrb and pluripotency factors along with marks of active genes. Mechanistically, we show Ncoa3 is specifically required to bridge RNApol2 to Esrrb. We thus identify a new member of the ES pluripotency network and describe Esrrb and Ncoa3 as key factors linking core pluripotency factors to the general transcription machinery. ChIP experiments were carried out with chromatin prepared from E14 cells as previously described (Stock et al., 2007), using 8-10 ug primary antibody for NcoA3 and 600 ug pre-cleared chromatin per IP. Antibody for NcoA3 was from Santacruz (sc-9119) .

2012-10-02 | E-GEOD-37262 | biostudies-arrayexpress

Global gene expression analysis of Ncoa3 knockdown in mouse embryonic stem cells

Project description:Orphan nuclear receptor Esrrb is vital in maintaining ES cells and like Oct4, Sox2 and Nanog is essential for self-renewal and pluripotency. Esrrb functions in somatic cells via LBD/AF-2-dependent coactivator recruitment to target genes. Here we show that in ES cells coactivator recruitment is similarly required and identify Ncoa3 as the Esrrb coactivator needed for activation of its target genes. Ncoa3 is essential for self-renewal and the induction of pluripotency in reprogramming, and genome-wide analysis of Ncoa3 binding reveals extensive overlap with Esrrb and pluripotency factors along with marks of active genes. Mechanistically, we show Ncoa3 is specifically required to bridge RNApol2 to Esrrb. We thus identify a new member of the ES pluripotency network and describe Esrrb and Ncoa3 as key factors linking core pluripotency factors to the general transcription machinery. Three biological replicates each for control scrambled shRNA and Ncoa3 shRNA transfected E14 mouse ESCs. The global gene expression profiles of Ncoa3 knockdown cells were compared to control scrambled shRNA knockdown cells 4 days post-transfection.

2012-10-02 | E-GEOD-40192 | biostudies-arrayexpress

Global gene expression analysis of Ncoa3 knockdown in mouse embryonic stem cells

2012-10-02 | GSE40192 | GEO

Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of Trophoblast Stem Cells

Project description:Esrrb is a transcription factor implicated in embryonic stem (ES) cell self-renewal, yet its knockout causes intrauterine lethality due to defects in trophoblast development. Here we show that in trophoblast stem (TS) cells, Esrrb is a downstream target of fibroblast growth factor (Fgf) signalling and is critical to drive TS cell self-renewal. In contrast to its occupancy of pluripotency-associated loci in ES cells, Esrrb sustains the stemness of TS cells by direct binding and regulation of TS cell-specific transcription factors including Elf5 and Eomes. To elucidate the mechanisms whereby Esrrb controls the expression of its targets, we characterized its TS cell-specific interactome by mass spectrometry. Unlike in ES cells, Esrrb interacts in TS cells with the histone demethylase Lsd1 and with the RNA Polymerase II-associated Integrator complex. Our findings provide new insights into both, the general and context-dependent wiring of transcription factor networks in stem cells by master transcription factors.

2015-07-24 | PXD002183 | Pride

Ncoa3 in mouse embryonic stem cells

Project description:This SuperSeries is composed of the following subset Series: GSE37262: A Nuclear Receptor Coactivator is Essential for Esrrb Activity and the Induction and Maintenance of the ES Cell State GSE40192: Global gene expression analysis of Ncoa3 knockdown in mouse embryonic stem cells Refer to individual Series

2012-10-02 | E-GEOD-40193 | biostudies-arrayexpress

Esrrb Regulates Specific Feed-Forward Loops to Transit from Pluripotency into Early Stages of Differentiation (RNA-Seq)

Project description:Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to be crucial for embryonic stem (ES) self-renewal maintenance and cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these state transitions remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of ES cells that incorporate protein-coding and miRNA genes based on microRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific ES cell miRNA expression program and integrates dynamic changes of feed forward loops contributing to the exit of the pluripotency state upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in stem cells.

2022-03-21 | GSE189678 | GEO

Esrrb Regulates Specific Feed-Forward Loops to Transit from Pluripotency into Early Stages of Differentiation

2022-03-21 | GSE57371 | GEO

Next generation unnatural monosaccharides reveal that ESRRBO GlcNAcylation enhances pluripotency of mouse embryonic stem cells

Project description:Unnatural monosaccharides such as azidosugars that can be metabolically incorporated into cellular glycans are currently used as a major tool for glycan imaging and glycoproteomic profiling. As a common practice to enhance membrane permeability and cellular uptake, the unnatural sugars are per O acetylated, which, however, can induce a long-overlooked side reaction, non enzymatic S-glycosylation. Herein, we develop1,3 di esterified N azidoacetylgalactosamine (GalNAz) as the next generation chemical reporters for metabolic glycan labeling. Both 1,3 di O-acetylated GalNAz (1,3-Ac2GalNAz) and1,3 di O propionylated GalNAz (1,3-Pr2GalNAz)exhibited high efficiency for labeling protein O-GlcNAcylation with no artificial S-glycosylation. Applying1,3 Pr2GalNAz in mouse embryonic stem cells (mESCs), we identified ESRRB, a critical transcription factor for pluripotency, as an O-GlcNAcylated protein. We showed that ESRRB O-GlcNAcylation is important for mESC self-renewal and pluripotency. Mechanistically, ESRRB is O-GlcNAcylated by O-GlcNAc transferase (OGT) at serine 25 (Ser 25), which stabilizes ESRRB, promotes its transcription activity and facilitates its interactions with two master pluripotency regulators, OCT4 and NANOG.

2019-09-12 | PXD014785 | Pride

Next generation unnatural monosaccharides reveal that ESRRBO GlcNAcylation enhances pluripotency of mouse embryonic stem cells

2019-09-09 | PXD015035 | Pride

Esrrb function in the extraembryonic ectoderm is required for proper primordial germ cell specification [microarray]

Project description:Estrogen related receptor beta (Esrrb) is an orphan nuclear receptor that is required for self-renewal and pluripotency in mouse embryonic stem (ES) cells. However, in the early post-implantation mouse embryo, Esrrb is specifically expressed in the extraembryonic ectoderm (ExE) and plays a crucial role in trophoblast development. In this study, to better understand the function of Esrrb in trophoblast lineage cells, we performed microarray analysis of Esrrb-null mutant versus wild-type mouse embryos. To further characterize the regulatory targets of Esrrb, we treated trophoblast stem (TS) cells with either Esrrb inhibitor DES or vehicle and compared their global gene expression profile via RNA-seq analysis. In addition, to ask whether these target genes are directly regulated by Esrrb, we performed Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis of TS cells using anti-Esrrb antibody.

2019-07-15 | GSE123360 | GEO

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