FIGURE 3 | Integrating chromatin and transcriptional information.

a | Polycomb repressor complex 2 (PRC2) contains the enhancer of zeste homologue 2 (EZH2) methyltransferase that methylates lysine 27 of histone H3 (H3K27) and is found at most of the repressed loci that are targeted by octamer-binding transcription factor 4 (OCT4), SRY-box 2 (SOX2) and NANOG in human embryonic stem (ES) cells⁶⁷. This implicates PRC2 in gene repression at these loci and indicates that OCT4, SOX2 or NANOG might recruit PRC2 to specific targets. However, PRC2 also binds at a range of promoters where the OCT4–SOX2–NANOG 'triad' do not bind, implying that other sequence-specific DNA-binding factors might also function in PRC2 recruitment in ES cells⁹⁶. b | Loss-of-function genetic screens have identified seven transcription factors that are required for stem-cell identity: OCT4, SOX2, NANOG, estrogen-related receptor- (ESRRB), T-box 3 (TBX3), T-cell lymphoma breakpoint 1 (TCL1) and developmental pluripotency associated 4 (DPPA4). These proteins directly (indicated by circles) or indirectly (indicated by triangles) regulate many genes. Activation (indicated in green) or repression (indicated in red) of a subset of genes depends only on OCT4, SOX2 and NANOG, regulation of a second cluster depends on ESRRB, TBX3, TCL1 and DPPA4, and the expression of a third subset depends on both groups of factors. These data indicate the presence of at least two independent pathways controlling stem-cell self-renewal.

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