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Series GSE42120 Query DataSets for GSE42120
Status Public on Nov 08, 2012
Title β-catenin regulates FSHβ induction by GnRH: next generation RNA-Sequencing identifies Brms1L as a mediator of beta-catenin regulation of FSHβ gene expression
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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 β-catenin in LHβ induction by GnRH has been discovered. We examined the role of β-catenin in FSHβ gene expression in LβT2 gonadotrope cells. GnRH caused a sustained increase in nuclear β-catenin levels, which was significantly reduced by JNK inhibition. siRNA-mediated knockdown of β-catenin mRNA demonstrated that induction of FSHβ mRNA by GnRH depended on β-catenin and that regulation of FSHβ by β-catenin occurred independently of the JNK-c-jun pathway. β-catenin depletion had no impact on FSHβ mRNA stability. In LβT2 cells transfected with FSHβ promoter luciferase fusion constructs, GnRH responsiveness was conferred by the proximal promoter (-944/-1), and was markedly decreased by β-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 β-catenin and the 1.8 kb FSHβ promoter. To elucidate the mechanism for the β-catenin effect, we analyzed ~1 billion reads of next generation RNA sequencing β-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 β-catenin knockdown as well as by JNK inhibition. Furthermore, knockdown of Brms1L significantly attenuated GnRH-induced FSHβ expression. Thus, our findings indicate that the expression of Brms1L depends on β-catenin activity and contributes to FSHβ induction by GnRH.
Overall design A total of 24 samples were analyzed, namely 6 different experimental conditions, each comprised of 4 replicates. Control samples are included in the analysis. For the RNA-Seq assay, samples were multiplexed in the form of 3 samples per lanes, resulting in a total of 8 lanes.
Contributor(s) Wang Q, Chikina M, Zaslavsky E, Pincas H, Sealfon SC
Citation(s) 23211523, 24591653, 29487567
Submission date Nov 07, 2012
Last update date May 15, 2019
Contact name Maria Chikina
Organization name Mount Sinai School of Medicine
Street address Annenberg 14-88 One Gustave Levy Pl
City New York
State/province NY
ZIP/Postal code 10029
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (24)
GSM1032773 Scr.siRNA+vehicle_1
GSM1032774 Scr.siRNA+vehicle_2
GSM1032775 Scr.siRNA+vehicle_3
BioProject PRJNA179158
SRA SRP017110

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE42120_RAW.tar 315.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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