The B-cell CLL/lymphoma 7 (BCL7) protein family members drive gene expression changes via interactions with the Brahma Related Gene 1 (BRG1) Helicase-Sant Associated domain (HSA) domain [BCL7 knockdown]. The B-cell CLL/lymphoma 7 (BCL7) protein family members drive gene expression changes via interactions with the Brahma Related Gene 1 (BRG1) Helicase-Sant Associated domain (HSA) domain [BCL7 knockdown]

The SWI/SNF complex remodels chromatin in an ATP-dependent manner through the ATPase subunits BRG1 and Brm Chromatin remodeling alters nucleosome structure to change gene expression. However, aberrant remodeling and gene expression can result in cancer. We identified a family of SWI/SNF complex members, the BCL7 proteins, as critical components to drive BRG1-dependent gene expression changes. The BCL7 proteins have been implicated in B-cell lymphoma, but the characterization of their functional role within the SWI/SNF complex has not been fully explored. This study implicates their critical function alongside BRG1 to cause large scale changes in gene expression. Mechanistically, the BCL7 proteins bind to the HSA domain of BRG1 and require this domain for stable protein expression and binding to chromatin. These results provide a link between the HSA domain and the formation of a stable functional SWI/SNF remodeling complex through the interaction with the BCL7 proteins. The data shown here highlights the importance of proper formation of the SWI/SNF complex to drive critical biological functions, as losses of members that were once considered minor accessory components can cause severe loss of complex function. Overall design: Adrenacorticoid carcinoma cells were generated to inducibly express respective constructs and harvested for RNA-seq.

SWI/SNF复合物（SWI/SNF complex）可通过其ATP酶亚基BRG1与Brm以ATP依赖的方式重塑染色质。染色质重塑通过改变核小体结构调控基因表达。然而，异常的染色质重塑与基因表达失调可诱发癌症。我们鉴定出SWI/SNF复合物的BCL7蛋白家族，其作为关键组分介导BRG1依赖的基因表达改变。既往研究已将BCL7蛋白与B细胞淋巴瘤相关联，但其在SWI/SNF复合物内的功能特性尚未得到全面解析。本研究证实，BCL7蛋白可与BRG1协同发挥关键功能，进而引发大规模的基因表达改变。从机制上看，BCL7蛋白可结合BRG1的HSA结构域，且该结构域是BCL7蛋白稳定表达以及结合染色质所必需的。本研究结果揭示了HSA结构域通过与BCL7蛋白相互作用，进而促成稳定且具备功能的SWI/SNF染色质重塑复合物形成的潜在关联。本研究展示的数据凸显了SWI/SNF复合物正确组装对于介导关键生物学功能的重要性——曾被视为次要辅助组分的复合物成员缺失，可导致复合物功能严重受损。总体实验设计：构建可诱导表达对应构建体的肾上腺皮质癌细胞系，收集细胞并开展RNA测序（RNA-seq）。