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Series GSE106653 Query DataSets for GSE106653
Status Public on Feb 13, 2019
Title GLP-1 signaling suppresses menin's transcriptional block by phosphorylation in beta cells
Organism Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Summary We find that GLP-1 signaling-activated PKA directly phosphorylates menin at serine 487 residue, relieving menin mediated suppression of insulin expression in beta cells and islets of diabetic GK rat. Mechanistically, GLP-1-induced PKA activation leads to menin Ser487 phosphorylation, and phosphorylated menin gains increased binding affinity to cytoskeleton proteins such as beta actin and myosin. Sequestration of Ser487 phosphorylated menin from the Ins1 gene promoter leads to reduced binding of menin-associating repressive epigenetic regulators such as SUV39H1 and HDAC1 at the locus, resulting in increased Ins1 transcription. Our results have linked GLP-1 signaling to physiologically suppression of menin function in repressing insulin expression, and uncovered a potential step to modulate menin phosphorylation to improve T2D therapy.
Overall design mRNA profiles of INS-1 cells overexpressing menin S487A or S487D mutant were generated by deep sequencing, in triplicate.
Contributor(s) Xing B
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Submission date Nov 07, 2017
Last update date May 15, 2019
Contact name Bowen Xing
Phone 86-13005411156
Organization name Shenzhen University
Street address Nanhai Street 3688
City Shenzhen
State/province Guangdong
ZIP/Postal code 518060
Country China
Platforms (1)
GPL18694 Illumina HiSeq 2500 (Rattus norvegicus)
Samples (6)
GSM2844569 INS-1 S487A 1
GSM2844570 INS-1 S487A 2
GSM2844571 INS-1 S487A 3
BioProject PRJNA417512
SRA SRP124536

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Supplementary file Size Download File type/resource
GSE106653_gene_exp.txt.gz 1.0 Mb (ftp)(http) TXT
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