Polycomb repressive complex 2 (PRC2) has a well characterised role in maintaining gene
silencing and is essential for normal development, tissue homeostasis and is frequently
dysregulated in cancer. The classical role of PRC2 is to catalyse post-translational
modification of histone tails, with tri-methylation of Histone 3 lysine 27 strongly associated
with gene silencing. Recent studies have highlighted additional non-classical roles for PRC2
including methylation of non-histone substrates, direct transcriptional activation and
association with cell signalling cascades. Here I show that loss of core PRC2 components
results in reduced Wnt signalling in embryonic stem cells (ESCs). Mouse ESCs that lack Suz12
show virtually undetectable canonical Wnt signalling. ESCs lacking Suz12 fail to differentiate.
Intriguingly, efficient downregulation of pluripotency genes, but failure of induction of
lineage specific genes is observed. In addition to the contribution to canonical Wnt signalling,
beta-catenin also complexes with E-cadherin at cell surface adherens junctions. Importantly,
altered E-cadherin localisation is observed in PRC2 null ES cells. E-cadherin localisation is
normalised at cell-cell contacts between PRC2 mutant and wild type ES cells when grown
together. Normalisation of E-cadherin localisation occurs concomitant to reestablishment of
canonical Wnt signalling, and rescue of neuronal differentiation.
The dual residency protein Afadin, a constituent of the intracellular adherens junction
complex is also shown to have altered subcellular localisation in the absence of Jarid2 or
Suz12. Taken together these results suggests a potential non-classical role for PRC2 in
regulation of the adherens junctions, which in turn modifies the contribution of cadherin
associated beta-catenin to Wnt signalling, and differentiation.