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A Long Noncoding RNA, lncRNA-Amhr2, Plays a Role in Amhr2 Gene Activation in Mouse Ovarian Granulosa Cells

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Title: A Long Noncoding RNA, lncRNA-Amhr2, Plays a Role in Amhr2 Gene Activation in Mouse Ovarian Granulosa Cells
Authors: Kimura, Atsushi P. Browse this author →KAKEN DB
Yoneda, Ryoma Browse this author
Kurihara, Misuzu Browse this author
Mayama, Shota Browse this author
Matsubara, Shin Browse this author
Keywords: Anti-Müllerian hormone type II receptor
transgenic mouse
long noncoding RNA
granulosa cell
reporter gene
Issue Date: 14-Nov-2017
Publisher: Oxford University Press
Journal Title: Endocrinology
Volume: 158
Issue: 11
Start Page: 4105
End Page: 4121
Publisher DOI: 10.1210/en.2017-00619
PMID: 28938492
Abstract: Anti-Mullerian hormone (AMH) is critical to the regression of Mullerian ducts during mammalian male differentiation and targets ovarian granulosa cells and testicular Sertoli and Leydig cells of adults. Specific effects of AMH are exerted via its receptor, AMH type II receptor (Amhr2), but the mechanism by which the Amhr2 gene is specifically activated is not fully understood. To see whether a proximal promoter was sufficient for Amhr2 gene activation, we generated transgenic mice that bore the enhanced green fluorescent protein (EGFP) gene driven by a 500-bp mouse Amhr2 gene promoter. None of the established 10 lines, however, showed appropriate EGFP expression, indicating that the 500-bp promoter was insufficient for Amhr2 gene activation. As a regulatory element, we found a long noncoding RNA, lncRNA-Amhr2, transcribed from upstream of the Amhr2 gene in ovarian granulosa cells and testicular Sertoli cells. In primary granulosa cells, knockdown of lncRNA-Amhr2 resulted in a decrease of Amhr2 messnger RNA level, and a transient reporter gene assay showed that lncRNA-Amhr2 activation increased Amhr2 promoter activity. The activity was correlated with lncRNA-Amhr2 transcription in stably transfected OV3121 cells derived from mouse granulosa cells. Moreover, by the Tet-on system, the induction of lncRNA-Amhr2 transcription dramatically increased Amhr2 promoter activity in OV3121 cells. These results indicate that lncRNA-Amhr2 plays a role in Amhr2 gene activation in ovarian granulosa cells by enhancing promoter activity, providing insight into Amhr2 gene regulation underlying the AMH signaling in the female reproductive system.
Type: article (author version)
Appears in Collections:理学院・理学研究院 (Graduate School of Science / Faculty of Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 木村 敦

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