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Epigenetics

Context-dependent role of SWI/SNF

Nature Reviews Cancer volume 14, page 9 (2014)Cite this article

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The SWI/SNF chromatin-remodelling complex suppresses tumours in many tissues. Shi et al. found that, in acute leukaemias, SWI/SNF complexes containing the ATPase subunit BRG1 (also known as SMARCA4) have an oncogenic function. BRG1 occupied lineage-specific enhancers clustered 1.7 Mb downstream of MYC in leukaemia cells and maintained MYC expression by sustaining transcription factor occupancy and allowing long-range interactions with the MYC promoter. This enhancer cluster is amplified in ∼3% of acute myeloid leukaemias, suggesting that it is functionally relevant in human leukaemias. Loss of BRG1 ATPase activity inhibited leukaemia cell proliferation, indicating that ATPase inhibition would be desirable therapeutically. However, targeting this activity would have to be balanced with the tumour-suppressing effects of BRG1 in other tissues.

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References

  1. Shi, J. et al. Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation. Genes Dev. http://dx.doi.org/10.1101/gad.232710.113 (2013)

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  1. Sarah Seton-Rogers
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Seton-Rogers, S. Context-dependent role of SWI/SNF. Nat Rev Cancer 14, 9 (2014). https://doi.org/10.1038/nrc3664

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