Knocking off their Sox: lineage-specific repression by Polycomb in epidermal stem cells

Abstract

EMBO J 32 14, 1990–2000 doi:; DOI: 10.1038/emboj.2013.110; published online May 14 2013

A recent publication in The EMBO Journal (Bardot et al, 2013) provides novel insights into lineage specification during the development of the mouse skin. Ezhkova and colleagues demonstrate that Ezh1 and Ezh2, core enzymes of the Polycomb Repressive Complex (PRC), restrict differentiation of Merkel cells, a specialized population of mechanosensory cells by directly repressing the cell fate determinant transcription factor (TF) Sox2 in epidermal progenitors.

Figure 1

In tissue progenitors, PRC complexes promote stem cell self-renewal by inhibiting various cell cycle regulators, such as INK4A/ARF/INK4B, E2F/RB, P21 and P57. In addition, in conjunction with other epigenetic pathways they keep transcription factors essential for lineage determination (depicted here as XY, Z and QT) repressed. Certain lineages (in this case Lineage 1) depend exclusively upon loss of PRC repression to upregulate fate determinants. However, most lineages are correctly specified even in the absence of PRC, suggesting that either they are independent of PRC or that they depend on additional epigenetic factors.