A collaborative team led by Bing Li from Shanghai Jiao Tong University School of Medicine published an article titled "BCL7A’s arginine anchor links nucleosome recognition to chromatin remodeling and diffuse large B-cell lymphoma tumor suppression" in Protein & Cell. This study demonstrates that the conserved arginine anchor within the N-terminal α-helix of BCL7A is crucial for its function across all genomic contexts. This anchor acts as a key molecular switch connecting nucleosome binding to chromatin remodeling and tumor suppression, positioning it as a potential therapeutic target for DLBCL.
Research Background
The human SWI/SNF (hSWI/SNF) chromatin remodeling complex plays a pivotal role in cell differentiation, development, and disease pathogenesis. Approximately 20% of human cancers are associated with mutations in one or more of the 30 genes encoding hSWI/SNF complex subunits. Chromatin remodelers often interact with nucleosomes via arginine anchors, yet the precise molecular mechanisms remain to be fully elucidated.
BCL7A is a tissue-specific, non-catalytic subunit of the hSWI/SNF complex with established tumor-suppressive activity, particularly notable in diffuse large B-cell lymphoma (DLBCL). However, the specific epigenetic molecular mechanism by which BCL7A, as a regulatory subunit of the chromatin remodeling complex, exerts these functions has remained largely unclear
Key Findings
(1) BCL7A employs distinct structural domains for complex assembly and nucleosome binding respectively: The study reveals that the β-sheet fold of BCL7A is responsible for its integration into the hSWI/SNF complex, while its N-terminal α-helix (containing the arginine anchor) directly binds nucleosomes and regulates chromatin remodeling activity. These two functions are separable, with the latter being essential for its tumor-suppressive function.
(2) BCL7A's arginine anchor is a key molecular switch for DLBCL tumor suppression: The nucleosome anchoring mediated by this domain not only influences chromatin accessibility and target gene transcription, but its loss or mutation completely abrogates tumor-suppressive capacity. Clinical data further confirms its high mutation frequency in DLBCL, underscoring its importance as a potential therapeutic target.
DOI:10.1093/procel/pwaf114