N-terminal arginine anchor in BCL7A Fine-tunes Chromatin Remodeling and Drives Tumor Suppression in DLBCL [ATAC-seq]

The hSWI/SNF (BRG1/BRM-associated factor) chromatin remodeling complex plays a critical role in regulating chromatin accessibility and gene expression, with its dysfunction linked to cancer. However, the specific mechanisms by which its subunit BCL7A suppresses tumor growth, particularly in diffuse large B-cell lymphoma (DLBCL), remain unclear. We hypothesized that the N-terminal α-helix of BCL7A, containing a conserved arginine anchor, mediates its interaction with the nucleosome acidic patch to regulate chromatin remodeling and tumor suppression. Our findings reveal that the arginine anchor is essential for BCL7A’s binding to the hSWI/SNF complex and its chromatin remodeling activity. Disruption of this anchor, either through truncation or recurrent DLBCL-associated mutations, abolishes BCL7A’s tumor-suppressive function without affecting its incorporation into the hSWI/SNF complex. Loss of the arginine anchor globally reduces BCL7A occupancy at target loci, impairing chromatin accessibility and transcriptional regulation. In vivo and cellular assays further confirm that the arginine anchor is critical for BCL7A-mediated suppression of tumor growth. This study identifies the BCL7A arginine anchor as a key molecular switch linking nucleosome binding to chromatin remodeling and tumor suppression, offering insights for targeted therapeutic strategies in DLBCL.