-catenin regulates FSH induction by GnRH: next generation RNA-Sequencing identifies Brms1L as a mediator of beta-catenin regulation of FSH gene expression
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| Accession | GSE42120 |
| Title | -catenin regulates FSH induction by GnRH: next generation RNA-Sequencing identifies Brms1L as a mediator of beta-catenin regulation of FSH gene expression |
| Description | The regulation of gonadotropin synthesis by GnRH (Gonadotropin-releasing hormone) plays an essential role in the neuroendocrine control of reproduction. The known signaling mechanisms involved in gonadotropin synthesis have been expanding. For example, involvement of -catenin in LH induction by GnRH has been discovered. We examined the role of -catenin in FSH gene expression in LT2 gonadotrope cells. GnRH caused a sustained increase in nuclear -catenin levels, which was significantly reduced by JNK inhibition. siRNA-mediated knockdown of -catenin mRNA demonstrated that induction of FSH mRNA by GnRH depended on -catenin and that regulation of FSH by -catenin occurred independently of the JNK-c-jun pathway. -catenin depletion had no impact on FSH mRNA stability. In LT2 cells transfected with FSH promoter luciferase fusion constructs, GnRH responsiveness was conferred by the proximal promoter (-944/-1), and was markedly decreased by -catenin knockdown. However, none of the TCF/LEF binding sites in that region were required for promoter activation by GnRH. Chromatin immunoprecipitation further corroborated the absence of direct interaction between -catenin and the 1.8 kb FSH promoter. To elucidate the mechanism for the -catenin effect, we analyzed ~1 billion reads of next generation RNA sequencing -catenin knockdown assays and selected the nuclear cofactor Brms1L as one candidate for further study. Subsequent experiments confirmed that Brms1L mRNA expression was decreased by -catenin knockdown as well as by JNK inhibition. Furthermore, knockdown of Brms1L significantly attenuated GnRH-induced FSH expression. Thus, our findings indicate that the expression of Brms1L depends on -catenin activity and contributes to FSH induction by GnRH. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42120 |
| Repository | Gene Expression Omnibus |
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