Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells

Mapping Genome Occupancy in Embryonic Stem Cells

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• Human ES Cell Quality Control
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• Data Analysis

The targets of Suz12 were also enriched for genes that encode components of signaling pathways (Figure 3A and Table S12). Current studies suggest that the transforming growth factor-beta (TGFβ), bone morphogenic protein (BMP), wingless-type MMTV integration site (Wnt), and fibroblast growth factor (FGF) signaling pathways that are required for gastrulation and lineage differentiation in the embryo are also essential for self-renewal and differentiation of ES cells in culture (Loebel et al., 2003; Molofsky et al., 2004; Mishra et al., 2005; Varga and Wrana, 2005). We noted that Suz12 occupied the promoters of multiple components of these pathways. Although most of these genes were occupied by Suz12 over a small portion of their promoters, a few were more notable because Suz12 occupied large portions of their genes and these loci contained highly conserved elements, as observed for the developmental regulators. This group contained members of the Wnt family (WNT1, WNT2, WNT6) as well as components of the TGFβ superfamily (BMP2, GDF6). Recent studies have shown that Wnt signaling plays a role in pluripotency and self-renewal in both mouse and human ES cells (Sato et al., 2004) and our results suggest that it is important to maintain specific family members in a repressed state in ES cells.