Polycomb-mediated repression during terminal differentiation: what don't you want to be when you grow up?

Abstract

Chromatin-modifying enzymes are known to be critical components for the correct differentiation of embryonic stem cells into specific lineages, such as neurons. Recently, the role of Polycomb group proteins has been studied in the specification and differentiation of muscle stem cells. In this perspective, we review a recent study by Juan and colleagues (pp. 789-794) in Genes & Development of the role of the polycomb group protein Ezh2 in muscle stem cells, and discuss the implications for general lineage restriction.

Figure 1.

Model for restriction of transcription factor binding and gene activation during cell lineage commitment. In this model, during cellular lineage commitment and differentiation, the genes activated by transcription factors are restricted by a variety of processes. (Top) We envision that chromatin structure and the occlusion of binding sequences by repressors will dictate the first level of restriction by making subsets of binding targets either accessible or inaccessible to transcription factors (inaccessible nucleosomes are shaded in dark gray, and accessible nucleosomes are shaded in light blue). (Bottom) Sequence motifs located in accessible chromatin domains can be bound by transcription factor complexes, but the silent state of associated genes may be retained by either repressive chromatin marks or the presence of inhibitors. The end result is a carefully modulated pattern of transcription factor activity that leads to the expression pattern of a differentiated cell type.