Figure 5 from MUC1-C Dictates PBRM1-Mediated Chronic Induction of Interferon Signaling, DNA Damage Resistance, and Immunosuppression in Triple-Negative Breast Cancer
Year: 2025
Type: other
Abstract: MUC1-C/PBRM1/IRF1 complexes induce chromatin accessibility and expression of the RIG-I, MDA5, and ISG15 genes. A, Candidate pathway enrichment plot for the IFNA response in BT-549 cells silenced for MUC1-C, IRF1, and PBRM1. B and C, Genome browser snapshots of ATAC-seq data from the RIG-I (B) and MDA5 (C) PLSs in BT-549/tet-MUC1shRNA cells treated with vehicle or DOX for 7 days (left). Chromatin was analyzed for accessibility by nuclease digestion (right). The results are expressed as the percentage of undigested chromatin (mean ± SD and individual values). D and E, Schema of the RIG-I (D) and MDA5 (E) genes with localization of a PLS upstream to the TSS. Soluble chromatin from BT-549/tet-MUC1shRNA cells treated with vehicle or DOX for 7 days was precipitated with a control IgG, anti–MUC1-C, anti-IRF1 and anti-PBRM1. The DNA samples were amplified by qPCR with primers for the RIG-I (D) and MDA5 (E) PLS regions. The results (mean ± SD and individual values) are expressed as relative fold enrichment as compared with that obtained with IgG (assigned a value of 1). F, Chromatin from BT-549/CshRNA and BT-549/PBRM1shRNA cells was analyzed for accessibility of the RIG-I and MDA5 PLS regions by nuclease digestion. The results are expressed as the percentage of undigested chromatin (mean ± SD and individual values). G, Genome browser snapshots of ATAC-seq data from the ISG15 PLS in BT-549/tet-MUC1shRNA cells treated with vehicle or DOX for 7 days (left). Chromatin was analyzed for accessibility by nuclease digestion (right). The results are expressed as the percentage of undigested chromatin (mean ± SD and individual values). H, Schema of the ISG15 gene with localization of a PLS upstream to the TSS. Soluble chromatin from BT-549/tet-MUC1shRNA cells treated with vehicle or DOX for 7 days was precipitated with a control IgG, anti-MUC1-C, anti-IRF1, and anti-PBRM1. The DNA samples were amplified by qPCR with primers for the ISG15 PLS region. The results (mean ± SD and individual values) are expressed as relative fold enrichment as compared with that obtained with IgG (assigned a value of 1). I, Chromatin from BT-549/CshRNA and BT-549/PBRM1shRNA cells was analyzed for accessibility of the ISG15 PLS region by nuclease digestion. The results are expressed as the percentage of undigested chromatin (mean ± SD and individual values). *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001.
Authors: Nami Yamashita, Yoshihiro Morimoto, Atsushi Fushimi, Rehan Ahmad, Atrayee Bhattacharya, Tatsuaki Daimon, Naoki Haratake, Yuka Inoue, Satoshi Ishikawa, Masaaki Yamamoto, Tsuyoshi Hata, Sayuri Akiyoshi, Qiang Hu, Tao Liu, Henry Withers, Song Liu, Geoffrey I. Shapiro, Tomoharu Yoshizumi, Mark D. Long, Donald Kufe
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4416764885