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Neurodevelopmental disorders

Epigenetic targets on the table

Nature Reviews Drug Discovery volume 16, page 677 (2017)Cite this article

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Previous studies have highlighted that FMRP regulates the translation of synaptic targets, but investigational therapies directed at these synaptic proteins have not proved fruitful. Therefore, for the current study, Korb et al. set out to identify alternative FMRP target proteins that might be involved in FXS pathophysiology.

Earlier work using next-generation sequencing had suggested that FMRP might also regulate the translation of proteins involved in epigenetic regulation. Such epigenetic regulators include chromatin-associated proteins, which modify the transcription of target genes by post-translational modification of histones, such as methylation. Here, Korb et al. showed that the levels of several chromatin-associated proteins, such as BRD4, were higher in cortical neurons taken from knockout mice lacking the FMRP gene (Fmr1−/− mice) than from wild-type mice.

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References

  1. Korb, E. et al. Excess translation of epigenetic regulators contributes to fragile X syndrome and is alleviated by Brd4 inhibition. Cell 170, 1209–1223 (2017)10.1016/j.cell.2017.07.033

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  1. Katie Kingwell
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Kingwell, K. Epigenetic targets on the table. Nat Rev Drug Discov 16, 677 (2017). https://doi.org/10.1038/nrd.2017.193

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