p-2S-SMAD2,3:SMAD4, CTNNB1, and TBPL2 bind FOXH1:SMAD3:EOMES gene

Stable Identifier
R-HSA-9754480
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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NODAL-SMAD2,3 signaling is crucial for induction of EOMES expression, as EOMES is absent in NODAL-deficient mouse embryos. NODAL signaling causes phosphorylation of SMAD2 which transits to the nucleus with SMAD4 and binds and activates expression of the EOMES gene. Beta-catenin (CTNNB1) activated by Wnt signaling binds the EOMES gene and interacts directly with SMAD2,3 to yield full activation of EOMES (Funa et al. 2015). The pluripotency factors OCT4 and NANOG have also been implicated in activation of EOMES expression (Teo et al. 2011, Funa et al. 2015). In mesendoderm cells derived from human embryonic stem cells, the basal transcription factor TBPL2 (TRF3) binds the EOMES gene (Liang et al. 2020). In mouse embryonic stem cells, FOXH1 and SMAD3 are pre-bound to the EOMES gene (inferred from mouse homologs in mesendoderm progenitors generated from embryonic stem cells in vitro).
Literature References
PubMed ID Title Journal Year
32448362 TATA box-binding protein-related factor 3 drives the mesendoderm specification of human embryonic stem cells by globally interacting with the TATA box of key mesendodermal genes

Zhang, P, Yang, HT, Bai, HJ, Liang, H, Huang, J

Stem Cell Res Ther 2020
21245162 Pluripotency factors regulate definitive endoderm specification through eomesodermin

Dunn, NR, Chng, Z, Trotter, MW, Vallier, L, Teo, AK, Ang, LT, Brown, S, Arnold, SJ, Robertson, EJ

Genes Dev. 2011
25921273 β-Catenin Regulates Primitive Streak Induction through Collaborative Interactions with SMAD2/SMAD3 and OCT4

Hess, K, Semb, H, Dietrich, N, Lerdrup, M, Funa, NS, Schachter, KA, Honoré, C, Ekberg, J, Hansen, K

Cell Stem Cell 2015
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