Gene interactions and pathways from curated databases and text-mining
Cell 2005, PMID: 16153702

Core transcriptional regulatory circuitry in human embryonic stem cells.

Boyer, Laurie A; Lee, Tong Ihn; Cole, Megan F; Johnstone, Sarah E; Levine, Stuart S; Zucker, Jacob P; Guenther, Matthew G; Kumar, Roshan M; Murray, Heather L; Jenner, Richard G; Gifford, David K; Melton, Douglas A; Jaenisch, Rudolf; Young, Richard A

The transcription factors OCT4, SOX2, and NANOG have essential roles in early development and are required for the propagation of undifferentiated embryonic stem (ES) cells in culture. To gain insights into transcriptional regulation of human ES cells, we have identified OCT4, SOX2, and NANOG target genes using genome-scale location analysis. We found, surprisingly, that OCT4, SOX2, and NANOG co-occupy a substantial portion of their target genes. These target genes frequently encode transcription factors, many of which are developmentally important homeodomain proteins. Our data also indicate that OCT4, SOX2, and NANOG collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops. These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal.

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Text Mining Data

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Manually curated Databases

  • FastForward regulation: SOX2 → TRIM22 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → HMG20A (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → CDX4 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → LBX1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → SIX2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → GSC (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → CREB3L4 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → IRX2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → OLIG3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → DLX5 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → DMRT1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → E2F3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → EGR3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → EN1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → FERD3L (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → ATF6 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → ZNF281 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → PTF1A (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → NR6A1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → HBP1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → FOXP1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → BHLHE22 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → GLI3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → HDAC2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → HNRNPA1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → HOXB1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → HOXB3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → APEX1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → ID1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → MEIS1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → ATF4 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → ATOH1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → NFYA (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → NKX2-2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → NOTCH1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → NRL (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → PAX6 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → POU2F1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → ZNF395 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → ARNTL2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → REST (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → RFX1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → RFX4 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → RXRG (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → SFPQ (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → HLTF (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → SNAPC1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → SNAPC3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → SOX5 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → SP2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → TAL1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → TBP (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → TCF7L2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → NKX2-1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → TLE1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → UBP1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → ZIC1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → NANOG (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → NR4A3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → BRIP1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → TEAD2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → HESX1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → MSC (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → HAND2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: SOX2 → CDK1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → TRIM22 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → HMG20A (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → CDX1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → LBX1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → IRX2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → DLX5 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → DMRT1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → EN1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → FERD3L (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → FGF3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → IKZF3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → ZHX2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → OTP (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → PTF1A (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → HMGB2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → FOXA2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → HOXA4 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → HOXA7 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → HOXB1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → HOXB6 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → HOXC12 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → ID2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → JUND (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → MEIS1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → ZFHX3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → NKX2-2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → SIX6 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → PAX6 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → PAX7 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → LEF1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → RFX4 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → ISL2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → SOX5 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → TAL1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → TCF4 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → TCF21 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → NKX2-1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → WT1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → NANOG (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → NR4A3 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → HESX1 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → MSC (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: POU5F1 → LHX2 (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • FastForward regulation: MEF2A → MYOG (transcriptional regulation, unknown)
    Evidence: DNABINDING
  • Reactome Reaction: SALL4 → SOX2 (direct_complex)
  • Reactome Reaction: SMAD4 → ZSCAN10 (reaction)
  • Reactome Reaction: POU5F1 → SOX2 (reaction)
  • Reactome Reaction: PRDM14 → ZSCAN10 (direct_complex)
  • Reactome Reaction: POU5F1 → PRDM14 (reaction)
  • Reactome Reaction: SMAD2 → NANOG (reaction)
  • Reactome Reaction: NANOG → ZSCAN10 (direct_complex)
  • Reactome Reaction: POU5F1 → NANOG (direct_complex)
  • Reactome Reaction: PBX1 → NANOG (reaction)
  • Reactome Reaction: POU5F1 → SMAD2 (reaction)
  • Reactome Reaction: PRDM14 → ZSCAN10 (reaction)
  • Reactome Reaction: POU5F1 → SMAD2 (indirect_complex)
  • Reactome Reaction: KLF4 → POU5F1 (direct_complex)
  • Reactome Reaction: POU5F1 → PRDM14 (direct_complex)
  • Reactome Reaction: PRDM14 → NANOG (direct_complex)
  • Reactome Reaction: NANOG → ZSCAN10 (reaction)
  • Reactome Reaction: POU5F1 → SOX2 (direct_complex)
  • Reactome Reaction: SMAD2 → ZSCAN10 (reaction)
  • Reactome Reaction: KLF4 → SMAD4 (indirect_complex)
  • Reactome Reaction: PBX1 → SOX2 (direct_complex)
  • Reactome Reaction: SMAD2 → ZSCAN10 (indirect_complex)
  • Reactome Reaction: SMAD2 → NANOG (indirect_complex)
  • Reactome Reaction: POU5F1 → NANOG (reaction)
  • Reactome Reaction: KLF4 → SMAD2 (indirect_complex)
  • Reactome Reaction: KLF4 → PBX1 (direct_complex)
  • Reactome Reaction: PBX1 → SMAD2 (indirect_complex)
  • Reactome Reaction: KLF4 → POU5F1 (reaction)
  • Reactome Reaction: SALL4 → ZSCAN10 (direct_complex)
  • Reactome Reaction: PBX1 → SMAD2 (reaction)
  • Reactome Reaction: SOX2 → ZSCAN10 (direct_complex)
  • Reactome Reaction: PRDM14 → SALL4 (direct_complex)
  • Reactome Reaction: PBX1 → POU5F1 (reaction)
  • Reactome Reaction: PBX1 → SMAD4 (reaction)
  • Reactome Reaction: POU5F1 → SALL4 (direct_complex)
  • Reactome Reaction: SMAD2 → SOX2 (reaction)
  • Reactome Reaction: KLF4 → SMAD2 (reaction)
  • Reactome Reaction: KLF4 → SOX2 (reaction)
  • Reactome Reaction: PBX1 → SOX2 (reaction)
  • Reactome Reaction: SOX2 → NANOG (direct_complex)
  • Reactome Reaction: POU5F1 → ZSCAN10 (reaction)
  • Reactome Reaction: SOX2 → NANOG (reaction)
  • Reactome Reaction: POU5F1 → SALL4 (reaction)
  • Reactome Reaction: SMAD4 → SOX2 (reaction)
  • Reactome Reaction: KLF4 → SOX2 (direct_complex)
  • Reactome Reaction: PBX1 → NANOG (direct_complex)
  • Reactome Reaction: PRDM14 → SOX2 (reaction)
  • Reactome Reaction: SOX2 → ZSCAN10 (reaction)
  • Reactome Reaction: SALL4 → SMAD2 (indirect_complex)
  • Reactome Reaction: SMAD4 → ZSCAN10 (indirect_complex)
  • Reactome Reaction: SALL4 → SOX2 (reaction)
  • Reactome Reaction: PRDM14 → SMAD2 (reaction)
  • Reactome Reaction: POU5F1 → SMAD4 (reaction)
  • Reactome Reaction: SALL4 → ZSCAN10 (reaction)
  • Reactome Reaction: POU5F1 → SMAD4 (indirect_complex)
  • Reactome Reaction: PRDM14 → SALL4 (reaction)
  • Reactome Reaction: POU5F1 → ZSCAN10 (direct_complex)
  • Reactome Reaction: KLF4 → SMAD4 (reaction)
  • Reactome Reaction: PRDM14 → SMAD4 (reaction)
  • Reactome Reaction: PBX1 → SMAD4 (indirect_complex)
  • Reactome Reaction: SALL4 → SMAD4 (indirect_complex)
  • Reactome Reaction: SALL4 → SMAD4 (reaction)
  • Reactome Reaction: KLF4 → NANOG (direct_complex)
  • Reactome Reaction: KLF4 → NANOG (reaction)
  • Reactome Reaction: PRDM14 → SMAD4 (indirect_complex)
  • Reactome Reaction: PBX1 → POU5F1 (direct_complex)
  • Reactome Reaction: SALL4 → NANOG (reaction)
  • Reactome Reaction: SMAD2 → SOX2 (indirect_complex)
  • Reactome Reaction: SMAD4 → NANOG (reaction)
  • Reactome Reaction: PRDM14 → NANOG (reaction)
  • Reactome Reaction: SMAD4 → SOX2 (indirect_complex)
  • Reactome Reaction: SMAD4 → NANOG (indirect_complex)
  • Reactome Reaction: SALL4 → SMAD2 (reaction)
  • Reactome Reaction: SALL4 → NANOG (direct_complex)
  • Reactome Reaction: PRDM14 → SOX2 (direct_complex)
  • Reactome Reaction: KLF4 → PBX1 (reaction)
  • Reactome Reaction: PRDM14 → SMAD2 (indirect_complex)
In total, 145 gene pairs are associated to this article in curated databases