Mammalian SWI/SNF (mSWI/SNF) adenosine triphosphate–dependent chromatin remodelers modulate genomic architecture and gene expression and are frequently mutated in disease. However, the specific chromatin features that govern their nucleosome binding and remodeling activities remain unknown. We subjected endogenously purified mSWI/SNF complexes and their constituent assembly modules to a diverse library of DNA-barcoded mononucleosomes, performing more than 25,000 binding and remodeling measurements. Here, we define histone modification-, variant-, and mutation-specific effects, alone and in combination, on mSWI/SNF activities and chromatin interactions. Further, we identify the combinatorial contributions of complex module components, reader domains, and nucleosome engagement properties to the localization of complexes to selectively permissive chromatin states. These findings uncover principles that shape the genomic binding and activity of a major chromatin remodeler complex family.

哺乳动物 SWI/SNF (mSWI/SNF) 三磷酸腺苷依赖性染色质重塑剂调节基因组结构和基因表达，并且经常在疾病中发生突变。然而，控制其核小体结合和重塑活动的特定染色质特征仍然未知。我们将内源性纯化的 mSWI/SNF 复合物及其组成组装模块置于多样化的 DNA 条形码单核小体文库中，执行超过 25,000 次结合和重塑测量。在这里，我们定义了组蛋白修饰、变体和突变特异性效应，单独和组合，对 mSWI/SNF 活性和染色质相互作用。此外，我们确定了复杂模块组件、阅读器域、和核小体结合特性将复合物定位到选择性允许的染色质状态。这些发现揭示了塑造主要染色质重塑复合物家族的基因组结合和活性的原理。