730 THE ROLE OF JARID1A IN SPERMATOGENESIS EVALUATION OF TRANSCRIPTIONAL REGULATION BY HISTONE H3K4 METHYLATION

Abstract

You have accessJournal of UrologyPediatrics: Basic Research1 Apr 2012730 THE ROLE OF JARID1A IN SPERMATOGENESIS EVALUATION OF TRANSCRIPTIONAL REGULATION BY HISTONE H3K4 METHYLATION Hidenori Nishio, Yoshiyuki Kojima, Yoshinobu Moritoki, Makoto Imura, Hideyuki Kamisawa, Atsushi Okada, Kentaro Mizuno, Yukihiro Umemoto, Keiichi Tozawa, Yutaro Hayashi, and Kenjiro Kohri Hidenori NishioHidenori Nishio Nagoya, Japan More articles by this author , Yoshiyuki KojimaYoshiyuki Kojima Nagoya, Japan More articles by this author , Yoshinobu MoritokiYoshinobu Moritoki Nagoya, Japan More articles by this author , Makoto ImuraMakoto Imura Nagoya, Japan More articles by this author , Hideyuki KamisawaHideyuki Kamisawa Nagoya, Japan More articles by this author , Atsushi OkadaAtsushi Okada Nagoya, Japan More articles by this author , Kentaro MizunoKentaro Mizuno Nagoya, Japan More articles by this author , Yukihiro UmemotoYukihiro Umemoto Nagoya, Japan More articles by this author , Keiichi TozawaKeiichi Tozawa Nagoya, Japan More articles by this author , Yutaro HayashiYutaro Hayashi Nagoya, Japan More articles by this author , and Kenjiro KohriKenjiro Kohri Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.815AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Spermatogenesis, a fundamental process in the male reproductive system, requires a series of tightly controlled epigenetic and genetic events in germ cells ranging from spermatogonia to spermatozoa. We recently reported that important differentiation occurs in the testes of rats at approximately 9 days. We observed through microarray gene expression analysis that Jumonji, AT rich interactive domain 1A (Jarid1a) was highly expressed in the undescended testes compared with normal testes at 9 days. The purpose of this study was to examine the effects of Jarid1a, a key epigenetic regulator expressed in the testis, on spermatogenesis. METHODS We injected flutamide (7.5 mg/day per body) into the abdomen of pregnant rats for 7 days from the 14th to 20th day of gestation to obtain offspring with undescended testes. Nine-day-old male rats were divided into 3 groups: (1) f-UDT, offspring with undescended testes, (2) f-DT, offspring with descended testes, and (3) nD9, normal testes of normal rats. Jarid1a gene expression in these 3 groups was assessed by real-time polymerase chain reaction (RT-PCR) and western blot. The localization of expression was assessed by immunohistochemistry. Moreover, these groups were assessed by western blot using the anti-histone H3 lysine 4 (H3K4) antibody and methylated antibody to evaluate the state of H3K4 modification. RESULTS RT-PCR study showed that Jarid1a was significantly expressed in the f-UDT compared to f-DT or nD9. Similar findings were observed by western blot study analysis. Immunohistochemical analysis showed that Jarid1a was expressed in the nuclei from Ad spermatogonia to spermatids. Furthermore, western blot analysis of H3K4 methylation showed that levels of dimethylated H3K4 (H3K4me2) and tri-methylated H3K4 (H3K4me3) were higher in f-UDT than in f-DT or nD9. CONCLUSIONS Jarid1a belongs to the Jumonji family, whose members share the Jumonji C (JmjC) domain and suppress transcription by means of demethylating tri- and di-methylated H3K4. Because Jarid1a was expressed in rat testes in widespread spermatogenesis and was especially high in early spermatogenesis, the state of methylation of H3K4 highly correlates with spermatogenesis. Jarid1a demethylase-regulated histone modification is likely to inhibit spermatogenesis via a low level of methylated H3K4 in undescended testes. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e300 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hidenori Nishio Nagoya, Japan More articles by this author Yoshiyuki Kojima Nagoya, Japan More articles by this author Yoshinobu Moritoki Nagoya, Japan More articles by this author Makoto Imura Nagoya, Japan More articles by this author Hideyuki Kamisawa Nagoya, Japan More articles by this author Atsushi Okada Nagoya, Japan More articles by this author Kentaro Mizuno Nagoya, Japan More articles by this author Yukihiro Umemoto Nagoya, Japan More articles by this author Keiichi Tozawa Nagoya, Japan More articles by this author Yutaro Hayashi Nagoya, Japan More articles by this author Kenjiro Kohri Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...