Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

Single-Cell Multiomic Profiling of GATA3–BRG1 Interactions During Mesenchymal-to-Epithelial Transition in TNBC

GATA3 is a transcription factor that suppresses metastasis in invasive breast cancer, yet its mechanism of chromatin remodeling remains unclear. We hypothesize that GATA3 requires cooperation with chromatin remodelers such as BRG1, a SWI/SNF complex ATPase to facilitate mesenchymal-to-epithelial transition (MET) and reprogramming in aggressive breast cancer cells. Using MDA-MB-231 triple-negative breast cancer cells with a doxycycline-inducible GATA3 expression system and shRNA BRG1 knockdown system, we evaluated the effects of GATA3 induction and BRG1 knockdown on cell state. We performed single-cell multiomic analysis (10x Genomics RNA-seq and ATAC-seq) to simultaneously profile transcriptional changes and chromatin accessibility. The data reveal that BRG1 is required for GATA3-mediated MET. Induction of GATA3 triggers luminal/epithelial gene expression and chromatin remodeling consistent with MET only in the presence of functional BRG1. Loss of BRG1 negates the MET program even with GATA3 induction. These findings highlight a pioneer factor role for GATA3 that operates co-factorly with BRG1 to remodel chromatin. This work provides new insight into chromatin remodeling mechanisms during MET and suggests the therapeutic potential of targeting the GATA3-BRG1 axis in invasive breast cancer.