Knockout human reveal an essential role for Paternally Expressed 10 (PEG10) in JEG3 cell line development
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66304 | GEO | 2018/02/24
REPOSITORIES: GEO
Similar Datasets
Project description:The goal of this study was to determine transcriptional changes in HEK293 cells upon overexpression of various forms of Paternally Expressed Gene 10, or PEG10. Cells were transfected either with control, or with PEG10 gag, gag-pol, or isolated NC fragment constructs and RNA isolated for RNA-Seq analysis.
2023-03-29 | GSE227789 | GEO
Project description:The prevailing dogma that approximately 50% of our genome is “junk” DNA composed of transposable elements and retroviral insertions has recently been challenged. It has become evident that our genome has taken advantage of these transposable elements and uses them as a source of DNA to generate novel genes, which subsequently allow the organism to evolve. This process is termed “domestication of transposable elements” and the majority of these genes have been found to be essential for the existence of the organism. One of these developmentally essential domesticated genes: Peg10 (paternally expressed gene 10), was derived from a Ty3/gyspy LTR retrotransposon, yet lost its ability to transpose due to mutational events during its domestication. Remarkably, Peg10 has successfully maintained its Gag and Pol-like domains for millions of years. Peg10 orthologues are expressed in eutherian mammals and are essential for placentogenesis. To address the functional mechanisms of Peg10 we studied it in Trophoblast Stem Cells (TSCs). We find that the Gag of Peg10 is fully active: it promotes budding of vesicles, akin to the viral counterpart that catalyzes the budding of viruses. TSCs, deleted for Peg10, fail to differentiate into placental lineages, underscoring a critical role in lineage specification. This paper discusses our efforts to characterize the contents of Peg10 vesicles and whether such vesicles regulate lineage specification.
2019-03-22 | GSE122215 | GEO
Project description:The prevailing dogma that approximately 50% of our genome is “junk” DNA composed of transposable elements and retroviral insertions has recently been challenged. It has become evident that our genome has taken advantage of these transposable elements and uses them as a source of DNA to generate novel genes, which subsequently allow the organism to evolve. This process is termed “domestication of transposable elements” and the majority of these genes have been found to be essential for the existence of the organism. One of these developmentally essential domesticated genes: Peg10 (paternally expressed gene 10), was derived from a Ty3/gyspy LTR retrotransposon, yet lost its ability to transpose due to mutational events during its domestication. Remarkably, Peg10 has successfully maintained its Gag and Pol-like domains for millions of years. Peg10 orthologues are expressed in eutherian mammals and are essential for placentogenesis. To address the functional mechanisms of Peg10 we studied it in Trophoblast Stem Cells (TSCs). We find that the Gag of Peg10 is fully active: it promotes budding of vesicles, akin to the viral counterpart that catalyzes the budding of viruses. TSCs, deleted for Peg10, fail to differentiate into placental lineages, underscoring a critical role in lineage specification. This paper discusses our efforts to characterize the contents of Peg10 vesicles and whether such vesicles regulate lineage specification.
2019-03-22 | GSE122216 | GEO
Project description:Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease characterized by motor neuron dysfunction and loss, leading to progressive paralysis and death. A portion of ALS cases is caused by mutation of the proteasome shuttle factor Ubiquilin 2 (UBQLN2), but the molecular pathway leading from UBQLN2 dysfunction to neurodegenerative disease remains unclear. Here, we demonstrate a major function of UBQLN2 in regulating activity of the domesticated gag-pol retrotransposon ‘paternally expressed gene 10’ (PEG10) in human cells and tissues. UBQLN2 exclusively facilitates degradation of the frameshifted gag-pol form of PEG10 through recognition of a unique polyproline repeat. In cells, the PEG10 gag-pol protein cleaves itself in a mechanism reminiscent of retrotransposon self-processing to generate a liberated ‘nucleocapsid’ fragment, which uniquely localizes to the nucleus. Overexpression of the nucleocapsid fragment upregulates transcription of neuronal genes involved in axon remodeling, which were also affected in sporadic ALS (sALS) patient tissues. Finally, proteomics of spinal cords from ALS patients revealed that PEG10 gag-pol is significantly elevated in disease compared to healthy controls. These findings implicate the retrotransposon-like activity of PEG10 as a contributing mechanism in ALS through regulation of neuronal gene expression, and restraint of PEG10 as a primary function of UBQLN2.
2023-03-24 | PXD031964 | Pride
Project description:Peg10 (paternally expressed gene 10) is an imprinted gene that is essential for placental development (1). It is thought to derive from a Ty3-gyspy LTR (long terminal repeat) retrotransposon and retains Gag and Pol-like domains (2). Here we show that the Gag domain of PEG10 can promote vesicle budding similar to the HIV p24 Gag protein. Expressed in a subset of mouse endocrine organs in addition to the placenta, PEG10 was identified as a substrate of the deubiquitinating enzyme USP9X. Consistent with PEG10 having a critical role in placental development, PEG10-deficient trophoblast stem cells (TSCs) exhibited impaired differentiation into placental lineages. PEG10 expressed in wild-type, differentiating TSCs was bound to many cellular RNAs including Hbegf (Heparin-binding EGF-like growth factor), which is known to play an important role in placentation (3). Expression of Hbegf was reduced in PEG10-deficient TSCs suggesting that PEG10 might bind to and stabilize RNAs that are critical for normal placental development.
2018-12-14 | MSV000083229 | MassIVE
Project description:Neuroendocrine prostate cancer (NEPC) is proliferative, invasive, and untreatable. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. In this study we modeled the development of NEPC from conventional prostatic adenocarcinoma using a unique patient-derived xenograft and identified up-regulation of the placental gene PEG10. We found that the androgen receptor and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at different stages of NEPC development. In vitro, PEG10 promoted cell cycle progression from G0/G1 in the context of TP53 loss, and regulated Snail expression via TGF-β signaling to promote invasion. Finally we show in vivo proof of principal using antisense oligonucleotide that PEG10 is a novel therapeutic target for NEPC.
2015-01-05 | GSE59985 | GEO
Project description:Neuroendocrine prostate cancer (NEPC) is proliferative, invasive, and untreatable. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. In this study we modeled the development of NEPC from conventional prostatic adenocarcinoma using a unique patient-derived xenograft and identified up-regulation of the placental gene PEG10. We found that the androgen receptor and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at different stages of NEPC development. In vitro, PEG10 promoted cell cycle progression from G0/G1 in the context of TP53 loss, and regulated Snail expression via TGF-β signaling to promote invasion. Finally we show in vivo proof of principal using antisense oligonucleotide that PEG10 is a novel therapeutic target for NEPC.
2015-01-05 | GSE59984 | GEO
Project description:Neuroendocrine prostate cancer (NEPC) is proliferative, invasive, and untreatable. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. In this study we modeled the development of NEPC from conventional prostatic adenocarcinoma using a unique patient-derived xenograft and identified up-regulation of the placental gene PEG10. We found that the androgen receptor and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at different stages of NEPC development. In vitro, PEG10 promoted cell cycle progression from G0/G1 in the context of TP53 loss, and regulated Snail expression via TGF-β signaling to promote invasion. Finally we show in vivo proof of principal using antisense oligonucleotide that PEG10 is a novel therapeutic target for NEPC. Six patient-derived xenograft tumors from the LTL331 xenograft lineage (PMID: 24356420; http://www.livingtumorcentre.com/) after differing lengths of time post-host castration. No replicates.
2015-01-05 | E-GEOD-59985 | biostudies-arrayexpress
Project description:Peg10 regulation of TSC differentiation
| PRJNA504005 | ENA
Project description:Neuroendocrine prostate cancer (NEPC) is proliferative, invasive, and untreatable. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. In this study we modeled the development of NEPC from conventional prostatic adenocarcinoma using a unique patient-derived xenograft and identified up-regulation of the placental gene PEG10. We found that the androgen receptor and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at different stages of NEPC development. In vitro, PEG10 promoted cell cycle progression from G0/G1 in the context of TP53 loss, and regulated Snail expression via TGF-? signaling to promote invasion. Finally we show in vivo proof of principal using antisense oligonucleotide that PEG10 is a novel therapeutic target for NEPC. 14 patient-derived xenograft tumors from the LTL331 xenograft lineage (PMID: 24356420; http://www.livingtumorcentre.com/) after differing lengths of time post-host castration. Three replicates present for days 1-3 post-host castration.
2015-01-05 | E-GEOD-59984 | biostudies-arrayexpress