OTX2 sustains a bivalent-like state of OTX2-bound promoters in medulloblastoma by maintaining their H3K27me3 levels

@article{Bunt2012OTX2SA,
  title={OTX2 sustains a bivalent-like state of OTX2-bound promoters in medulloblastoma by maintaining their H3K27me3 levels},
  author={J. Bunt and Nancy A. Hasselt and D. Zwijnenburg and J. Koster and R. Versteeg and M. Kool},
  journal={Acta Neuropathologica},
  year={2012},
  volume={125},
  pages={385-394}
}
Recent studies showed frequent mutations in histone H3 lysine 27 (H3K27) demethylases in medulloblastomas of Group 3 and Group 4, suggesting a role for H3K27 methylation in these tumors. Indeed, trimethylated H3K27 (H3K27me3) levels were shown to be higher in Group 3 and 4 tumors compared to WNT and SHH medulloblastomas, also in tumors without detectable mutations in demethylases. Here, we report that polycomb genes, required for H3K27 methylation, are consistently upregulated in Group 3 and 4… Expand
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TLDR
OTX2-binding sequences are depleted near TSSs in the genome, providing an explanation for the observed bi-modal distribution of OTX2 binding and suggesting an important functional interaction between OTX 2 and MYC in regulating gene expression in medulloblastoma. Expand
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It is hypothesized that the imbalance in cell cycle stimulation by OTX2 leads to cellular senescence either by activating the P53 pathway or through the induction of secretory factors. Expand
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TLDR
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TLDR
Observations suggest that OTX2 is essential for the pathogenesis of anaplastic medulloblastomas and that these tumors may be amenable to therapy with all-trans retinoic acid. Expand
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