Table 1.
Epigenetic Features and Transcription Factor Occupancy of Stem Cell Loci
| Gene ID | Function | Kim: 2008 (mES) Boyer: 2005 (hES) | Loh: 2006 (mES) | Marson: 2008 (mES) | Marson: 2008 SUZ12 | Ku: EZH2 (PRC2) | Ku: Suz12 (PRC2) | Ku: Ring1B (PRC1) | Ku: ESC Promoter State | Ku: NPC Promoter State | Ku: CpG (mES) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pou5f1 | TF activity | NOS | NO | NOST | – | – | – | – | K4 | None | ICP |
| Nanog | TF activity | NOS | NO | N | – | – | – | – | K4 | None | ICP |
| Sox2 | TF activity | NOS | NO | NOST | – | – | – | – | K4 | K4 | HCP |
| Osr2 | TF activity | NOS | – | NOST | Suz12 (CpG) | EZH2 | Suz12 | Ring1B | K4 + K27 | K4 | HCP |
| Olfml2a | ECM Binding | NOS | – | NO | – | – | – | – | K4 | None | HCP |
| Hist1h3i | DNA binding | NOS | – | NOST | – | – | – | – | K4 | K4 | HCP |
| Rest | Repressor | NOS | NO | NOS | – | – | – | – | K4 | None | HCP |
| Sfrp1 | Binding (Wnt) | NOS | – | NOST | Suz12 (CpG) | EZH2 | – | Ring1B | K4 + K27 | K27 | HCP |
| Zfp36l1 | TF activity | NOS | NO | NOST | – | – | – | – | K4 | K4 | HCP |
| Thbs2 | Structural | NOS | N | NOST | – | – | – | – | None | None | ICP |
| Ror1 | RTK activity | NOS | N | NOST | Suz12 (CpG) | EZH2 | – | – | K4 + K27 | K4 | HCP |
| Jarid2 | Repressor | NOS | NO | NOST | – | – | – | – | K4 | K4 | HCP |
| Zic5 | DNA binding | NOS | N | NOST | – | EZH2 | – | Ring1B | K4 | K4 | HCP |
| Rfx4 | DNA binding | NOS | NO | NOST | – | EZH2 | Suz12 | Ring1B | K4 + K27 | K4 | HCP |
| Lrrc2 | Protein Binding | NOS | NO | NOST | – | – | – | – | K4 | None | ICP |
| Spred1 | SCF-receptor | NOS | N | NOST | – | – | – | – | K4 | K4 | HCP |
| Fgfr2 | FGFR activity | NOS | N | NOST | – | EZH2 | Suz12 | Ring1B | K4 + K27 | K4 | HCP |
| Gad2 | E-decarboxylase | NOS | – | NOST | Suz12 (CpG) | EZH2 | Suz12 | Ring1B | K4 + K27 | None | HCP |
| Hoxb1 | TF activity | NOS | – | NOST | Suz12 (CpG) | EZH2 | Suz12 | Ring1B | K27 | K27 | HCP |
| Pipox | Oxidase | NOS | O | NOST | – | – | – | – | K4 | K4 | LC P |
| Grap2 | SH3/SH2 adaptor | NOS | O | NOST | – | – | – | – | None | None | LC P |
| Spic | TF activity | NOS | – | NOST | – | – | – | – | None | None | ICP |
| Hist1h1b | DNA binding | NOS | – | NOST | – | – | – | – | K4 | K4 | HCP |
| Rif1 | Binding | NOS | O | NOST | – | – | – | – | K4 | K4 | HCP |
| Lefty2 | TGFbetaR | NOS | – | NOST | – | – | – | – | K4 + K27 | None | HCP |
| Lrrtm3 | Protein Binding | NOS | – | NOST | Suz12 | – | Suz12 | – | K27 | K4 | ICP |
| Cripto1 | Growth Factor | NOS | NO | NOST | – | – | – | – | K4 | None | ICP |
| Neurog1 | TF activity | NOS | – | NOST | Suz12 (CpG) | EZH2 | Suz12 | Ring1B | K4 + K27 | K27 | HCP |
| Nkx2-2 | TF activity | NOS | – | NOST | Suz12 (CpG) | EZH2 | Suz12 | Ring1B | K27 | K4 | HCP |
| Pax6 | TF activity | NOS | – | NOST | Suz12 (CpG) | EZH2 | Suz12 | Ring1B | K4 + K27 | K4 | HCP |
| Zic2 | DNA binding | NOS | – | NOST | Suz12 (CpG) | EZH2 | Suz12 | Ring1B | K4 + K27 | K4 | HCP |
| Dkk1 | Transducer (Wnt) | NOS | O | NOST | Suz12 (CpG) | EZH2 | Suz12 | Uncl. | K4 + K27 | None | ICP |
| *ZFP42 | TF activity | NO | – | NOS | – | EZH2 | – | – | K4 | None | ICP |
To illustrate the convergence of pluripotency transcription factor networks with epigenetic processes, we selected a subset of ES cell genes identified as Oct4, Nanog, and Sox2 target genes in both human (Boyer et al., 2005) and mouse ES cells (Kim et al., 2008)
This dataset was then examined in independent datasets for promoter occupancy by Oct4, Nanog [99] and for Nanog, Oct4, SOX2, TCF4 and polycomb complexes [144], bivalent histone methylation marks (K4 and/or K27), and DNA promoter methylation classification [87]. *Zfp42/Rex1 is included for comparison (see Fig. 3).
Abbreviations: TF, transcription factor; N, Nanog; O, OCT4/Pou5f1; S, SOX2; T, TCF; –, not detected; Suz12/EZH2, PRC2; Ring1b, PRC1; K4, histone H3 lysine 4 trimethylation; K27, histone H3 lysine 27 trimethylation; HCP, high CpG promoter containing a 500 bp region with GC content ≥0.55, observed to expected CpG ratio ≥0.6; LCP, low CpG promoter containing no 500 bp region and with observed to expected CpG ratio ≥0.4 and ICP, intermediate CpG promoter, CpG distribution between HCP and LCP; ESC, embryonic stem cell; NPC, neural precursor cell.