DOI: 10.5061/dryad.9p8cz8wpr
title: PP2A complex disruptor SET prompts widespread hyper-transcription of growth-essential genes in the pancreatic cancer cells

description: Hyper-activation of the oncogenic transcription reflects the epigenetic
 plasticity of the cancer cells. SET was described as a nuclear factor that
 stimulated transcription from the chromatin template. However, the
 mechanisms of SET-dependent transcription are unknown. Here, we found that
 over-expression of SET and CDK9 induced very similar transcriptome
 signatures in multiple cancer cell lines. SET localized in the
 transcription start site (TSS)-proximal regions and supported the RNA
 transcription. SET specifically bound the PP2A-C subunit and induced
 PP2A-A subunit repulsion from the C subunit, which indicated the role of
 SET as a PP2A-A/C complex disruptor in the TSS-proximal regions. Through
 blocking PP2A activity, SET assisted CDK9 to maintain Pol II CTD
 phosphorylation and activated mRNA transcription. Our findings position
 SET as a key factor that modulates chromatin PP2A activity, promoting the
 oncogenic transcription in pancreatic cancer.
description: # PP2A complex disruptor SET prompts widespread hyper-transcription of
 growth-essential genes in the pancreatic cancer cells
 ## Usage notes This
 dataset contains the results of the SET protein complex analysis. It also
 provides the way to access other supplementary data of this research. ###
 Datasets included: 1\) SET protein complex analysis in the HEK293T cells
 1. 10 million HEK293T cells were stably transfected with the control and
 Myc-SET plasmids, respectively. 2. Magnetic beads conjugated with anti-SET
 antibody were added to the control and SET-OE cell lyastes. 3. The control
 SET and SET-OE associated proteins were immunoprecipitated with magnetic
 beads and subjected to SDS-PAGE separation. 4. Thermo UltiMate 3000 UHPLC
 was utilized to separate samples of dried peptides. The liquid phase
 chromatography-separated peptides were ionized by a nanoESI source and
 passed to a tandem mass spectrometer Q-Exactive HF X for Data Dependent
 Acquisition mode detection. 5. For each detectable peptide of the SET
 associated proteins in the control and SET-OE cells, the iBAQ value was
 calculated and shown with the Protein ID in the datasheet (see the
 worksheet named "HEK293T" in the appended Excel file). 2\) SET
 protein complex analysis in the Panc02 cells 1. 10 million Panc02 cells
 were stably transfected with the control and SET overexpressing
 lentivirus, respectively. 2. Magnetic beads conjugated with anti-SET
 antibody were added to the control and SET-OE cell lyastes. 3. The control
 SET and SET-OE associated proteins were immunoprecipitated with magnetic
 beads and subjected to SDS-PAGE separation. 4. Thermo UltiMate 3000 UHPLC
 was utilized to separate samples of dried peptides. The liquid phase
 chromatography-separated peptides were ionized by a nanoESI source and
 passed to a tandem mass spectrometer Q-Exactive HF X for Data Dependent
 Acquisition mode detection. 5. For each detectable peptide of the SET
 associated proteins in the control and SET-OE cells, the iBAQ value was
 calculated and shown with the Protein ID in the datasheet (see the
 worksheet named "Panc02" in the appended Excel file). 3\) The
 other high-throughput sequencing results associated with the research. ##
 Sharing/Access information Alternatively, we have deposited the
 supplementary data including this IP-MS results, nascent RNA-seq, RNA-seq,
 ChIP-seq and CUT&Tag data reported in this paper to Mendeley Data
 (). ## Code/Software No new code or software in this research.