Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality

Ono, Ryuichi; Nakamura, Kenji; Inoue, Kimiko; Naruse, Mie; Usami, Takako; Wakisaka-Saito, Noriko; Hino, Toshiaki; Suzuki-Migishima, Rika; Ogonuki, Narumi; Miki, Hiromi; Kohda, Takashi; Ogura, Atsuo; Yokoyama, Minesuke; Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

doi:10.1038/ng1699

Cited by 395 publications

(361 citation statements)

References 27 publications

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“…PEG10 is also overexpressed in the embryonic form of biliary atresia, a disease associated with cell proliferation (Zhang et al, 2004). PEG10 À/À mice show early embryonic lethality owing to defects in the placenta, indicating a critical role for mouse parthenogenetic development (Ono et al, 2006). PEG10 knockdown inhibits the proliferation of pancreatic carcinoma and HepG2 HCC cells .…”

Section: Introductionmentioning

confidence: 99%

Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells

Xiong

Chen

et al. 2007

Oncogene

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The molecular mechanism of striking higher prevalence of hepatocellular carcinoma (HCC) in male subjects has not yet been fully elucidated. Here, we report that androgen receptor (AR) is differentially expressed in different HCC cell lines. AR agonist dihydrotestosterone (DHT) enhances HCC cell growth and apoptotic resistance. Antagonist flutamide (FLU) blocks the effects of DHT on the HCC cell lines. Paternally expressed gene 10 (PEG10) is expressed in HCC cell lines at substantial high level. Using small interfering RNAs against AR and PEG10 in AR-and PEG10-expressing BEL-7404 hepatoma cells and HuH7 hepatoma cells (HuH7) cells, and AR-transfection technique in AR-lacking and PEG10-expressing HepG2 cells, we have confirmed that through upregulation and activation of PEG10, DHT enhances HCC cell growth and apoptotic resistance. We have further demonstrated that DHT upregulates expression of human telomerase reverse transcriptase (hTERT) in HCC cell lines in a PEG10-dependent manner. Moreover, AR directly interacts in vivo with androgen-responsive elements in the regions of promoter and exon 2 of PEG10 gene in HCC cell lines. DHT promotes the hepatoma formation in vivo nude mice through PEG10 activation. AR antagonists (FLU and valproate) inhibit the hepatoma formation. These findings suggest that PEG10 plays an essential role in hepatocarcinogenesis. The PEG10 inhibition can be a novel approach for therapy of HCC.

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Section: Introductionmentioning

confidence: 99%

Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells

Xiong

Chen

et al. 2007

Oncogene

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“…Strikingly, a number of placenta-specific genes have appeared in the course of mammalian evolution through the recruitment of existing TE sequences, illustrating their central role in speciation. The placenta-essential Rtl1 and Peg10 genes evolved in mice from TE sequences of the Sushi-ichi class that are still present in the Fugu genome but are no longer active in mammals (Ono et al, 2006). Coincidently, syncytin genes have occurred independently in different mammalian lineages from ERVs, and have an essential role in placenta development and function (Heidmann (Wei et al, 2006;Bourque et al, 2008).…”

Section: Good Tes Bad Tesmentioning

confidence: 99%

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

2010

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Retrotransposable elements comprise around 50% of the mammalian genome. Their activity represents a constant threat to the host and has prompted the development of adaptive control mechanisms to protect genome architecture and function. To ensure their propagation, retrotransposons have to mobilize in cells destined for the next generation. Accordingly, these elements are particularly well suited to transcriptional networks associated with pluripotent and germinal states in mammals. The relaxation of epigenetic control that occurs in the early developing germline constitutes a dangerous window in which retrotransposons can escape from host restraint and massively expand. What could be observed as risky behavior may turn out to be an insidious strategy developed by germ cells to sense retrotransposons and hold them back in check. Herein, we review recent insights that have provided a detailed picture of the defense mechanisms that concur toward retrotransposon silencing in mammalian genomes, and in particular in the germline. In this lineage, retrotransposons are hit at multiple stages of their life cycle, through transcriptional repression, RNA degradation and translational control. An organized cross-talk between PIWIinteracting small RNAs (piRNAs) and various nuclear and cytoplasmic accessories provides this potent and multilayered response to retrotransposon unleashing in early germ cells.

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“…PEG10 shows parent-of-origin-specific expression in monochromosomal hybrids (21). PEG10 knockout mice show early embryonic lethality owing to defects in the placenta, indicating a critical role for mouse parthenogenetic development (21).…”

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confidence: 99%

CXC Chemokine Ligand 13 and CC Chemokine Ligand 19 Cooperatively Render Resistance to Apoptosis in B Cell Lineage Acute and Chronic Lymphocytic Leukemia CD23+CD5+ B Cells

et al. 2006

The Journal of Immunology

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CXCL13/CXCR5 and CCL19/CCR7 play a quite important role in normal physiological conditions, but the functions of both chemokine/receptor pairs in pathophysiological events are not well-investigated. We have investigated expression and functions of CXCL13/CXCR5 and CCL19/CCR7 in CD23+CD5+ and CD23+CD5− B cells from cord blood (CB) and patients with B cell lineage acute or chronic lymphocytic leukemia (B-ALL or B-CLL). CXCR5 and CCR7 are selectively expressed on B-ALL, B-CLL, and CB CD23+CD5+ B cells at high frequency, but not on CD23+CD5− B cells. Although no significant chemotactic responsiveness was observed, CXCL13 and CCL19 cooperatively induce significant resistance to TNF-α-mediated apoptosis in B-ALL and B-CLL CD23+CD5+ B cells, but not in the cells from CB. B-ALL and B-CLL CD23+CD5+ B cells express elevated levels of paternally expressed gene 10 (PEG10). CXCL13 and CCL19 together significantly up-regulate PEG10 expression in the same cells. We have found that CXCL13 and CCL19 together by means of activation of CXCR5 and CCR7 up-regulate PEG10 expression and function, subsequently stabilize caspase-3 and caspase-8 in B-ALL and B-CLL CD23+CD5+ B cells, and further rescue the cells from TNF-α-mediated apoptosis. Therefore, we suggest that normal lymphocytes, especially naive B and T cells, use CXCL13/CXCR5 and CCL19/CCR7 for migration, homing, maturation, and cell homeostasis as well as secondary lymphoid tissues organogenesis. In addition, certain malignant cells take advantages of CXCL13/CXCR5 and CCL19/CCR7 for infiltration, resistance to apoptosis, and inappropriate proliferation.

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Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality

Cited by 395 publications

References 27 publications

Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells

Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

CXC Chemokine Ligand 13 and CC Chemokine Ligand 19 Cooperatively Render Resistance to Apoptosis in B Cell Lineage Acute and Chronic Lymphocytic Leukemia CD23+CD5+ B Cells

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