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| Status |
Public on Jan 17, 2019 |
| Title |
PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells (RNA-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The PLZF transcription factor is essential for osteogenic differentiation of hMSCs, however, its regulation and molecular function during this process is not fully understood. Here we revealed that the ZBTB16 locus encoding PLZF, is repressed by Polycomb (PcG) and H3K27me3 in naïve hMSCs. At the pre-osteoblast stage of differentiation, the locus lost PcG binding and H3K27me3, gained JMJD3 recruitment, and H3K27ac resulting in high expression of PLZF. Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. The increased expression of NNMT correlated with a decline in SAM levels, which is dependent on PLZF and is required for osteogenic differentiation.
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| |
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| Overall design |
Effect of PLZF knockdown on osteogenic differentiation of hMSC (RNAseq)
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| |
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| Contributor(s) |
Agrawal Singh S, Lerdrup M, Gomes AR, Van de Werken HJ, Vilstrup Johansen J, Andersson R, Sandelin A, Helin K, Hansen K |
| Citation(s) |
30672466 |
| |
| Submission date |
Jan 16, 2019 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Mads Lerdrup |
| E-mail(s) |
[email protected]
|
| Phone |
+45 23636776
|
| Organization name |
University of Copenhagen
|
| Department |
Department of Cellular and Molecular Medicine
|
| Lab |
Center for Chromosome Stability
|
| Street address |
Blegdamsvej 3C
|
| City |
Copenhagen N |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE125168 |
PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells |
|
| Relations |
| BioProject |
PRJNA515466 |
| SRA |
SRP179743 |
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