PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells
2019
textabstractThe 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
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