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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| Overall design |
1)ChIP-seq on mouse MIN6 cells and islets
2)RNAseq on control and beta cell-specific Med15 knockout islets
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| Web link |
https://www.nature.com/articles/s41467-024-52801-9
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| 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 |
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| Submission date |
Sep 09, 2019 |
| Last update date |
Dec 10, 2024 |
| Contact name |
Francis C Lynn |
| E-mail(s) |
fclynn@interchange.ubc.ca
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| Phone |
6048752000
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| Organization name |
University of British Columbia
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| Department |
Surgery
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| Lab |
Lynn
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| Street address |
950 28th Ave W
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| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z 4H4 |
| Country |
Canada |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (31)
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| GSM4071985 |
Input_MIN6_rep2 |
| GSM4071986 |
Med15_MIN6_rep2 |
| GSM4071987 |
Med1_MIN6_rep2 |
| GSM4071988 |
Input_MIN6_rep3 |
| GSM4071989 |
Med15_MIN6_rep3 |
| GSM4071990 |
Med1_MIN6_rep3 |
| GSM4071991 |
Input_CTRL_rep1 |
| GSM4071992 |
Med15_CTRL_rep1 |
| GSM4071993 |
Med1_CTRL_rep1 |
| GSM4071994 |
Input_IM15KO_rep1 |
| GSM4071995 |
Med15_IM15KO_rep1 |
| GSM4071996 |
Med1_IM15KO_rep1 |
| GSM4071997 |
Input_CTRL_rep2 |
| GSM4071998 |
Med15_CTRL_rep2 |
| GSM4071999 |
Med1_CTRL_rep2 |
| GSM4072000 |
Input_IM15KO_rep2 |
| GSM4072001 |
Med15_IM15KO_rep2 |
| GSM4072002 |
Med1_IM15KO_rep2 |
| GSM8499617 |
islets, wildtype, rep1 |
| GSM8499618 |
islets, knockout, rep1 |
| GSM8499619 |
islets, wildtype, rep2 |
| GSM8499620 |
islets, knockout, rep2 |
| GSM8499621 |
islets, knockout, rep3 |
| GSM8499622 |
islets, wildtype, rep3 |
| GSM8499623 |
islets, knockout, rep4 |
| GSM8499624 |
islets, wildtype, rep4 |
| GSM8499625 |
islets, knockout, rep5 |
| GSM8499626 |
islets, wildtype, rep5 |
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| Relations |
| BioProject |
PRJNA564631 |
| SRA |
SRP221151 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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