PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells
| Title: | PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells |
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| Authors: | Shuchi Agrawal Singh, Mads Lerdrup, Ana-Luisa R Gomes, Harmen JG van de Werken, Jens Vilstrup Johansen, Robin Andersson, Albin Sandelin, Kristian Helin, Klaus Hansen |
| Source: | eLife, Vol 8 (2019) |
| Publisher Information: | eLife Sciences Publications Ltd, 2019. |
| Publication Year: | 2019 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | human mesenchymal stem cells, histone H3 lysine 27 tri-methylation, osteogenesis, developmental enhancer, Polycomb proteins, PLZF, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | 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 naive 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/40364; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.40364 |
| Access URL: | https://doaj.org/article/2c7c464f81894c2a99ba1da3eb3405fb |
| Accession Number: | edsdoj.2c7c464f81894c2a99ba1da3eb3405fb |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.40364 |
| Published in: | eLife |
| Language: | English |