Stem cell differentiation control

This is not easy stuff ,but if read slowly drinking a cup of tea ,can be at the very least comprehended. Again a complex system controlled by a methylation process.
The stem cell complex is capable of differentiating into most if not all tissues. The differentiation is determined by histone modification . Histones are the protein wrapping around the DNA.
Bone and fat are somewhat different and their formation involves osteoblasts and adipocytes respectively. The production of osteoblasts and adipocytes from common mesenchymal stem cells is under transcriptional control. Peroxisome proliferator receptor-γ is an marrow . inducer of fat tissue formation
Takada and colleagues have shown that a pathway using CaMKII-TAKl-TAB2-NLK transcriptionally represses PPAR-γ transactivation and induces Runx2 expression, promoting osteoblastogenesis in preference to adipogenesis in bone marrow mesenchymal progenitors. Wnt-5a activates NLK (Nemo-like kinase), which in turn phosphorylates a histone methyltransferase, SETDB1 (SET domain bifurcated 1), leading to the formation of a co-repressor complex that inactivates PPAR-γ function through histone H3-K9 methylation. The signalling pathway suppresses PPAR-γ function through chromatin inactivation triggered by recruitment of a repressing histone methyl transferase, thus leading to an osteobtastic cell lineage from mesenchymal stem cells.
Takarda et al 2007 A histone lysine methyltransferase activated by a non-canonical Wnt signalling suppresses PPAR-γ trans activation. .Nature Cell Biology 9, 1273-1285

Martin Eastwood
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