the effect of knockout Brd7 on 4T07-TGL cells under in vitro condition

Metastasis is a major cause of mortality in cancer and is likely influenced by epigenetic and gene regulatory factors. Using an in vivo screen, we demonstrated that several subunits of the polybromo-associated BAF (PBAF) complex, particularly BRD7, were required for breast cancer metastatic dormancy in lung. BRD7 loss induced metastatic outgrowth, along with modifications in epigenomic landscapes and upregulated oncogenic signaling. Breast cancer cells harboring BRD7 loss also reprogrammed the surrounding immune microenvironment, downregulating MHC-1 expression and promoting a pro-metastatic cytokine profile. Flow cytometric and single-cell analyses revealed increased levels of pro-tumorigenic neutrophils, CD8+ exhausted T cells, and CD4+ stress response T cells in lungs harboring BRD7-deficient metastases. Finally, attenuating this immunosuppressive milieu by neutrophil depletion, neutrophil extracellular trap (NET) inhibition, or immune checkpoint therapy abrogated metastatic outgrowth. These findings, for the first time, implicate BRD7 and PBAF in metastasis, pointing to targetable underlying mechanisms involving specific immune cell compartments. To study the function of PBAF subunit Brd7 in Breast cancer metastatic dormancy, we established Brd7 knockout 4T07-TGL cell lines by CRISPR/Cas9. To ascertain BRD7-dependent enhancer profiles in our 4T07 isogenics, we performed ChIP-seq for H3K27ac, a canonical enhancer mark, in our KO (Brd7-KO1, Brd7-KO2) and control (4T07-TGL-sgCtr) lines.