Human genomic DNA is packaged into chromatin, in which the basic repeating unit is the nucleosome, an assembly of ~147 DNA base pairs wound around a histone octamer core. Access to genetic information is tightly regulated by a group of proteins known as chromatin remodelers. We focus on the ATP-dependent Brg/Brahma Associated Factors (BAF) chromatin remodeling complex, composed of ~10-15 subunits and regulates diverse transcriptional cascades. Mutations in genes encoding subunits of the BAF complex are encountered in over 20% of human cancers, highlighting their relevance in human health. However, how the BAF complex recognizes distinct chromatin states, including histone post-translational modifications (PTMs), and the effects of cancer-associated mutations on BAF function remain poorly understood. Our goal is to functionally probe the mechanism by which the BAF complex dynamically moves on nucleosomal DNA and generate high-resolution structures of the human BAF complex bound to multiple distinct nucleosomal substrates. Understanding these interactions is crucial for comprehending BAF's role in regulating gene expression and cellular functions, potentially leading to novel therapeutic strategies for chromatin remodeling-related diseases.