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bioRxiv · 10.1101/2023.01.15.524091

Histone acetylation insulator SET orchestrates PP2A inhibition and super-enhancer activation

Wu, D.·Xu, H.·Xu, J.·Lei, Y.·Yu, X.·Shi, S.
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Abstract

Wide-spread growth-essential genes are hyper-transcribed in the pancreatic cancer cells. Searching for the factors that reprogram this abnormal transcription, we identified the nuclear oncogene SET that supported CDK9-induced and Pol II-mediated transcription. SET disrupted PP2A-A/C interaction via its C-terminal domains. Through blocking PP2A activity, SET assisted CDK9 to maintain Pol II CTD phosphorylation and activated mRNA transcription. Meanwhile, as a histone acetylation insulator, SET mainly suppressed histone acetylation in the gene promoters but evaded enhancers. Massive super-enhancer associated genes, including the oncogene MET, were hence permitted to be transcribed by SET over-expression. Our findings position SET as a key factor that bridges histone acetylation and PP2A related transcription in cancer cells.

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Wu, D., Xu, H., Xu, J., Lei, Y., Yu, X., Shi, S.. 2023-01-17. Histone acetylation insulator SET orchestrates PP2A inhibition and super-enhancer activation. https://doi.org/10.1101/2023.01.15.524091

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