PT  - JOURNAL ARTICLE
AU  - He Xu
AU  - Di Wu
AU  - Jin Xu
AU  - Yubin Lei
AU  - Yalan Lei
AU  - Xianjun Yu
AU  - Si Shi
TI  - Histone acetylation insulator SET orchestrates PP2A inhibition and super-enhancer activation
AID  - 10.1101/2023.01.15.524091
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.01.15.524091
4099  - http://biorxiv.org/content/early/2023/01/17/2023.01.15.524091.short
4100  - http://biorxiv.org/content/early/2023/01/17/2023.01.15.524091.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.