Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells

Mapping Genome Occupancy in Embryonic Stem Cells

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PRC2 is associated with an important set of developmental regulators that must be silent in ES cells but activated during differentiation. This observation suggests that PRC2 ultimately functions to repress occupied genes in ES cells and that these genes may be especially poised for transcriptional activation during ES cell differentiation. We reasoned that if this model is correct, genes bound by Suz12 should be preferentially activated upon ES cell differentiation or in cells that lack Suz12. Furthermore, in differentiated cells, Suz12 might continue to be observed at silent genes but must be removed from genes whose expression is essential for that cell type.

We first examined gene expression in ES cells stimulated to undergo differentiation (Sato et al., 2003). We found that genes occupied by Suz12 were more likely to be activated during ES cell differentiation than genes that were not occupied by Suz12 (Figure 6A; Supplemental Data, Table S13), indicating that Suz12-occupied genes show preferential activation during differentiation under these conditions. This effect was particularly striking at the set of developmental regulators (Figure 6B). Suz12 occupied most (83%) of the developmental regulators that were induced more than 10-fold during ES cell differentiation.

Suz12 occupies genes poised for expression during differentiation - Figure 6.

Relationship between size of Suz12 binding domain and RNA polymerase II co-occupancy and gene expression (Table S13).