RT Journal Article
SR Electronic
T1 Histone acetylation insulator SET orchestrates PP2A inhibition and super-enhancer activation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.15.524091
DO 10.1101/2023.01.15.524091
A1 He Xu
A1 Di Wu
A1 Jin Xu
A1 Yubin Lei
A1 Yalan Lei
A1 Xianjun Yu
A1 Si Shi
YR 2023
UL http://biorxiv.org/content/early/2023/01/17/2023.01.15.524091.abstract
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.