RRC ID 49318
Author Kimura AP, Yoneda R, Kurihara M, Mayama S, Matsubara S.
Title A Long Noncoding RNA, lncRNA-Amhr2, Plays a Role in Amhr2 Gene Activation in Mouse Ovarian Granulosa Cells.
Journal Endocrinology
Abstract Anti-Müllerian hormone (AMH) is critical to the regression of Müllerian 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.
Volume 158(11)
Pages 4105-4121
Published 2017-11-1
DOI 10.1210/en.2017-00619
PII 4158187
PMID 28938492
MeSH Animals Anti-Mullerian Hormone / metabolism Female Gene Expression Regulation Granulosa Cells / metabolism* Male Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Ovary / metabolism* Promoter Regions, Genetic RNA, Long Noncoding / physiology* Receptors, Peptide / genetics* Receptors, Peptide / metabolism Receptors, Transforming Growth Factor beta / genetics* Receptors, Transforming Growth Factor beta / metabolism Transcriptional Activation
IF 3.934
Times Cited 9
DNA material B6N Mouse BAC clone (RDB07573) B6Ng01-240N22.