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Series GSE137145 Query DataSets for GSE137145
Status Public on Sep 10, 2024
Title Transcriptional coactivator MED15 is required for beta cell maturation
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Mediator, a co-regulator required for RNA pol II activity, interacts with tissue-specific transcription factors to regulate development and maintain homeostasis. We sought to understand whether Mediator subunit MED15 acts as a node that controls tissue-specific gene expression, using pancreatic insulin-producing β-cell maturation as a model. We found Med15 to be expressed during mouse pancreatic organogenesis and β-cell maturation; moreover, islets from human T2D donors feature reduced MED15 expression. Loss of Med15 in mouse β-cells caused defects in maturation without affecting β-cell mass or insulin expression. ChIP-seq and co-immunoprecipitation analyses determined that Med15 binds β-cell transcription factors Nkx6-1 and NeuroD1 to regulate key β-cell maturation genes. Human embryonic stem cell derived β-like cells, genetically engineered to express high levels of MED15, had increased maturation markers and improved insulin secretion. We provide the first evidence of the importance of Mediator in β-cell maturation and demonstrate an additional layer of control that tunes transcription factor function.
 
Overall design 1)ChIP-seq on mouse MIN6 cells and islets
2)RNAseq on control and beta cell-specific Med15 knockout islets
Web link https://www.nature.com/articles/s41467-024-52801-9
 
Contributor(s) Kadhim AZ, Xu EE, Sasaki S, Cheng X, Winata H, Sproul SJ, Speckmann T, Nian C, Cullen R, Shi R, Winata H, Luciani DS, Hoffman BG, Taubert S, Lynn F
Citation(s) 39379383
Submission date Sep 09, 2019
Last update date Dec 10, 2024
Contact name Francis C Lynn
E-mail(s) fclynn@interchange.ubc.ca
Phone 6048752000
Organization name University of British Columbia
Department Surgery
Lab Lynn
Street address 950 28th Ave W
City Vancouver
State/province BC
ZIP/Postal code V5Z 4H4
Country Canada
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (31)
GSM4071982 Input_MIN6_rep1
GSM4071983 Med15_MIN6_rep1
GSM4071984 Med1_MIN6_rep1
Relations
BioProject PRJNA564631
SRA SRP221151

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SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE137145_20160511_DESeq2_normalized_Med15.csv.gz 1.7 Mb (ftp)(http) CSV
GSE137145_KO_Med1.bigwig 409.3 Mb (ftp)(http) BIGWIG
GSE137145_KO_Med15.bigwig 335.3 Mb (ftp)(http) BIGWIG
GSE137145_Med1.bigwig 38.3 Mb (ftp)(http) BIGWIG
GSE137145_Med15.bigwig 77.4 Mb (ftp)(http) BIGWIG
GSE137145_WT_Med1.bigwig 364.0 Mb (ftp)(http) BIGWIG
GSE137145_WT_Med15.bigwig 392.9 Mb (ftp)(http) BIGWIG
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Raw data are available in SRA
Processed data are available on Series record

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