Given that therapies based on polycomb repression are already being advanced as possible treatments of several BAF mutation–driven cancers, it has become important to understand the underlying mechanism of opposition between these complexes. Studies using in vitro transcription on nucleosomal templates are insufficient because they do not reproduce the domains of polycomb-mediated repression found over genes such as Sox2 in most somatic cell types. In addition, these in vitro techniques cannot detect the effects of long-range interactions, tissue-specific epigenetic changes, occurrence of histone H1, and a wide variety of other critical aspects of chromatin regulation. Hence, a major goal for the future will be to generate systems in which one lets the cell assemble chromatin with all its complexity and then challenges this locus with specific chromatin modifiers. This objective led us to develop a system for studying the complex chromatin regulation in different cell types using a mouse with an indicator and an array of regulatory sites knocked into the Oct4 gene (113). This system allows one to study the dynamic behavior of the locus, the rate of heterochromatin
