Fig. 3.

Normal Function of the SWItch/Sucrose Non-Fermentable (SWI/SNF) Complex and Mechanisms of Tumorigenesis. SWItch/Sucrose Non-Fermentable–related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1 (SMARCB1) is a subunit of the SWI/SNF complex, a dynamic chromatin remodeling complex that is necessary for normal cell differentiation and lineage determination. The SWI/SNF complex functions by binding specific chromatin-bound enhancers, elongating neighboring stretches of DNA and exposing them to transcription factors that guide normal cell differentiation and regulate self-renewal. In the absence of a functional SMARCB1 subunit, less SWI/SNF complex is available, the complex is not appropriately recruited to typical enhancers, and the remaining complex is recruited to super enhancers. In the absence of a functional SMARCB1 subunit, control of cell lineage determination is lost and multiple oncogenic pathways are disinhibited.