BRG1 promotes transcriptional patterns that are permissive to proliferation in cancer cells

• DOI: 10.1101/2020.07.03.187385
• Publication Date: 2020-07-05T04:15:12Z
• Authors: Katherine A. Giles; Cathryn M. Gould; Joanna Achinger-K...; Scott G. Page; Georgia Kafer; Phuc-Loi Luu; Anthony J. Cesare; Susan J. Clark; Phillippa C. Tabe...
• Keywords: SMARCA4; FOXA1; SWI/SNF

ABSTRACT Background BRG1 (encoded by SMARCA4 ) is a catalytic component of the SWI/SNF chromatin remodelling complex, with key roles in modulating DNA accessibility. Dysregulation observed, but functionally uncharacterised, wide range malignancies. We have probed functions on background prostate cancer to investigate how controls gene expression programs and cell behaviour. Results Our investigation revealed that universally overexpressed 486 tumours from The Cancer Genome Atlas cohort, as well complementary panel 21 lines. Next, we utilised temporal model depletion molecular effects global transcription programs. Unexpectedly, depleting had no impact alternative splicing conferred only modest effect expression. However, transcriptional changes occurred, most manifested down-regulated Deeper examination found common thread linking genes was involvement proliferation, including several known increase proliferation ( KLK2 , PCAT1 VAV3 ). Interestingly, promoters driving were bound oncogenic factors, AR FOXA1. also noted repressed involved cycle progression replication intriguingly, these pathways operated independently In agreement changes, G1 arrest. Conclusions data has capacity drive oncogenesis coordinating dependent for replication.