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| Status |
Public on Oct 14, 2013 |
| Title |
Extended self-renewal and accelerated reprogramming in the absence of Kdm5b [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
ES cell pluripotency is thought to be regulated in part by H3K4 methylation. However, it is unclear how H3K4 demethylation contributes to ES cell function and participates in iPS cell reprogramming. Here, we show that KDM5B, which demethylates H3K4, is important for ES cell differentiation, and presents a barrier to the reprogramming process. Depletion of Kdm5b leads to an extension in the self-renewal of ES cells in the absence of LIF. Transcriptome analysis revealed the persistent expression of pluripotency-genes and underexpression of developmental genes during differentiation in the absence of Kdm5b, suggesting that KDM5B plays a key role in cellular fate changes. We also observed accelerated reprogramming of differentiated cells in the absence of Kdm5b, demonstrating that KDM5B is a barrier to the reprogramming process. Expression analysis revealed that mesenchymal master regulators associated with epithelial-to-mesenchymal transition (EMT) are downregulated during reprogramming in the absence of Kdm5b. Moreover, global analysis of H3K4me3/2 revealed that enhancers of fibroblast genes are rapidly deactivated in the absence of Kdm5b, and genes associated with EMT lose H3K4me3/2 during the early reprogramming process. These findings provide functional insight into the role for KDM5B in regulating ES cell differentiation and as a barrier to the reprogramming process.
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| Overall design |
ChIP-Seq for H3K4me3 and H3K4me2 in murine shLuc and shKdm5b 4TF-MEFs (tetO-Pou5f1,-Sox2,-Klf4,-c-Myc) at 48h.
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| |
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| Contributor(s) |
Kidder BL, Hu G, Zhao K |
| Citation(s) |
24100015 |
| Submission date |
May 21, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Benjamin L Kidder |
| E-mail(s) |
benjamin.kidder@wayne.edu
|
| Organization name |
Wayne State University
|
| Department |
Oncology
|
| Lab |
Laboratory of Epigenomics
|
| Street address |
4100 John R St
|
| City |
Detroit |
| State/province |
MI |
| ZIP/Postal code |
48201 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE46893 |
Extended self-renewal and accelerated reprogramming in the absence of Kdm5b |
|
| Relations |
| BioProject |
PRJNA203696 |
| SRA |
SRP022934 |
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