-catenin regulates FSH induction by GnRH: next generation RNA-Sequencing identifies Brms1L as a mediator of beta-catenin regulation of FSH gene expression
Transcriptomics Dataset
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AccessionGSE42120
Title-catenin regulates FSH induction by GnRH: next generation RNA-Sequencing identifies Brms1L as a mediator of beta-catenin regulation of FSH gene expression
DescriptionThe 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 Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42120
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Dataset Accession

ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset

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Interactive heatmap visualization of RNA-seq dataset GSE42120
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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