The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus

Sugimoto, Kazunori; Kage, Hidenori; Aki, Naomi; Sano, Atsushi; Kitagawa, Hiroshi; Nagase, Takahide; Yatomi, Yutaka; Ohishi, Nobuya; Takai, Daiya

doi:10.1016/j.bbrc.2007.05.136

Cited by 75 publications

(68 citation statements)

References 27 publications

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“…INK4a gene and decreased p16 INK4a expression, 40 suggesting that PIWIL4 may be a regulator of p16 INK4a , a known regulator of adipocyte proliferation, differentiation, and senescence. 41 TAOK3 activates p38, inhibits cJun NH 2 -terminal kinase (JNK) signaling, 42 and is a member of the mitogen activated protein kinase (MAPK) cascade, affecting fundamental cellular signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Genome wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood

Huang

Davis

Garratt

et al. 2014

Obesity Research & Clinical Practice

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Section: Discussionmentioning

confidence: 99%

Genome wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood

Huang

Davis

Garratt

et al. 2014

Obesity Research & Clinical Practice

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“…In particular, Piwi would be responsible for the nuclear import of piRNAs and mediate epigenetic events (Klattenhoff and Theurkauf 2008). In mammals, Miwi and Mili are localized in cytoplasmic granules, when present in ovary and testis (Grivna et al 2006;Houwing et al 2007;Kuramochi-Miyagawa et al 2008), while Miwi2 in testis is nuclear , as are the human Piwi-like proteins in HEK 293 cells (Sugimoto et al 2007). For Piwi proteins to fulfill their epigenetic role, they presumably at least temporarily reside in the nucleus, while the current model of piRNA biogenesis would require their presence in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of Piwi proteins in Drosophila is seen both in the germline as well as in somatic cells (Cox et al 1998;Nishida et al 2007), while in vertebrates, significant expression has only been documented in the germline (Kuramochi-Miyagawa et al 2001;Qiao et al 2002;Tan et al 2002;Lau et al 2006;Carmell et al 2007;Houwing et al 2007;Sugimoto et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Two Piwi proteins, Xiwi and Xili, are expressed in the Xenopus female germline

Wilczynska

Minshall²,

Armisen³

et al. 2009

RNA

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The Argonaute superfamily is a large family of RNA-binding proteins involved in gene regulation mediated by small noncoding RNA and characterized by the presence of PAZ and PIWI domains. The family consists of two branches, the Ago and the Piwi clade. Piwi proteins bind to 21-30-nucleotide-long Piwi-interacting RNAs (piRNAs), which map primarily to transposons and repeated sequence elements. Piwi/piRNAs are important regulators of gametogenesis and have been proposed to play roles in transposon silencing, DNA methylation, transcriptional silencing, and/or post-transcriptional control of translation and RNA stability. Most reports to date have concentrated on the Piwi family members in the male germline. We have identified four Piwi proteins in Xenopus and demonstrate that two, namely, Xiwi1b and Xili, are expressed in the oocyte and early embryo. Xiwi1 and Xili are predominantly found in small, separate complexes, and we do not detect significant interaction of Piwi proteins with the cap-binding complex. Putative nuclear localization and export signals were identified in Xiwi1 and Xili, supporting our observation that Xiwi1, but not Xili, is a nucleo-cytoplasmic protein. Furthermore, by immunoprecipitation of small RNAs, we establish Xiwi1 as a bona fide Piwi protein. These results suggest that the Piwi/piRNA pathway is active in translationally repressed oocytes. This is a significant finding as the Xenopus model provides an excellent tool to study post-transcriptional mechanisms.

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“…Within the family, four members of the PIWI-like family, PIWIL1, PIWIL2, PIWIL3 and PIWIL4, have been identified in humans in previous reports, while in the mouse, there are only three Piwi subfamily genes, piwil1, piwll2 and piwil4 (32)(33)(34)(35). In regards to piwil4 and its tissue distribution, research has mainly focused on its role in spermatogensis (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Icariin induces apoptosis in mouse MLTC-10 Leydig tumor cells through activation of the mitochondrial pathway and down-regulation of the expression of piwil4

Xie¹

2011

Int J Oncol

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Abstract. The Leydig cell tumor, derived from interstitial cells, is a rare neoplasm. In most cases, Leydig cell tumors are benign, however, if the tumor is malignant, no effective treatments are currently available. In this study, we aimed to evaluate the effects of icariin on the growth of the mouse Leydig tumor cell line MLTC-1 and to examine its underlying mechanism. Icariin caused a dose-dependent decrease in the viability of MLTC-1 cells, which coincided with an increase in cell apoptosis through regulation of the expression of Bcl-2/Bax and cytochrome c, activation of caspase-9 and -3. Moreover, the pro-apoptotic effect of icariin on MLTC-1 cells is related to piwil4, since icariin induced a decrease in piwil4 protein expression and piwil4 silencing significantly enhanced the cytotoxic effects of icariin in MLTC-1 cells. These findings suggest a novel anticancer effect of icariin in Leydig cell tumor through activation of the mitochondrial pathway and down-regulation of the expression of piwil4. IntroductionTesticular neoplasms include germ cell tumors and sex cord-stromal tumors. Germ cell tumors comprise 95% of all testicular neoplasms, while the remaining 5% of testicular tumors are sex cord-stromal tumors, which are derived from somatic cells, Sertoli and Leydig cells. The Leydig cell tumor is classified as an interstitial cell tumor, which are commonly benign; however, in adults, ~10% of cases are malignant (1-4). The etiology of Leydig cell tumor in humans remains unknown. Currently, in most cases, the standard therapy for benign Leydig cell tumors is considered to be orchiectomy. Recently, by retrospectively analyzing the long-term follow-up of a series of patients with Leydig cell tumors electively treated with testis sparing surgery, Glannarin et al (5) demonstrated that testis sparing surgery with frozen section examination has an excellent long-term oncological outcome. Therefore, testis-sparing surgery may be chosen for treating benign Leydig cell tumors to maintain fertility, especially in boys and young men (5-9). If the tumor is malignant, orchiectomy with retroperitoneal lymph node dissection is recommended, since chemotherapy and radiation therapy show limited efficacy in the treatment of malignant Leydig cell tumors. Survival time of patients with this malignancy range from 2 months to 17 years, and the mean survival time is 2 years (10,11). To improve the survival time of patients with malignant Leydig cell tumor, and to decrease the serious consequences, such as testicular dysfunction and infertility that is caused by the current treatment for benign Leydig cell tumors, alternative treatments need to be explored.Icariin (C 33 H 40 O 15 ; molecular weight, 676.67), a flavonoid isolated from Herba Epimedii, is considered to be the main active component responsible for the actions of Herba Epimedii. Many studies have shown that it has a wide range of pharmacological and biological activities on endocrine, cardiovascular, genital, bronchial, urinary and immune systems (12)(13)(14)(15). In ...

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The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus

Cited by 75 publications

References 27 publications

Genome wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood

Genome wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood

Two Piwi proteins, Xiwi and Xili, are expressed in the Xenopus female germline

Icariin induces apoptosis in mouse MLTC-10 Leydig tumor cells through activation of the mitochondrial pathway and down-regulation of the expression of piwil4

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