PP2A complex disruptor SET prompts widespread hypertranscription of growth-essential genes in the pancreatic cancer cells

• DOI: 10.1126/sciadv.adk6633
• Publication Date: 2024-01-26T18:58:19Z
• Authors: He Xu; Di Wu; Mingming Xiao; Yubin Lei; Yalan Lei; Xianjun Yu; Si Shi
• Keywords: RNA polymerase II; Transcription; Pioneer factor

Hyperactivation of the oncogenic transcription reflects epigenetic plasticity cancer cells. Su(var)3-9, enhancer zeste, Trithorax (SET) was described as a nuclear factor that stimulated from chromatin template. However, mechanisms SET-dependent are unknown. Here, we found overexpression SET and CDK9 induced very similar transcriptome signatures in multiple cell lines. localized start site (TSS)–proximal regions supported RNA transcription. specifically bound PP2A-C subunit PP2A-A repulsion C subunit, which indicated role PP2A-A/C complex disruptor TSS-proximal regions. Through blocking PP2A activity, assisted to maintain Pol II CTD phosphorylation activated mRNA Our findings position key modulates promoting pancreatic cancer.