Oncogenic transformation can be caused by the imbalance between the opposing functions of BAF and Polycomb, for instance, at the Ink4a locus in rhabdoid tumor (Wilson et al., 2010) and at the Sox2 locus in synovial sarcoma (Kadoch and Crabtree, 2013). It is possible that a direct mechanistic link also exists between the two chromatin regulators in human neurological disorders. To this end, it is worth noting that mutations in EZH2 cause Weaver’s syndrome (Gibson et al., 2012; Tatton-Brown et al., 2013; Tatton-brown et al., 2011), a developmental disorder which presents with macrocephaly, in contrast to the microcephalic phenotype seen in BAF-related neurodevelopmental disorders. Polycomb inhibits Wnt signaling to antagonize the neurogenic fate of neural precursors (Hirabayashi et al., 2009), while BAF complexes have been shown to interact directly with β-catenin to activate Wnt target genes in a colon carcinoma cell line (Barker et al., 2001). Thus, one of the rate-limiting regulatory mechanisms in neural development and homeostasis may be the opposition between BAF and Polycomb complexes.
