p-2S-Smad2,3:Smad4 bind Foxh1:Smad3:Eomes gene

Stable Identifier
R-MMU-9754488
Type
Reaction [binding]
Species
Mus musculus
Compartment
nucleoplasm
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
p-2S-Smad2,3:Smad4 bind Foxh1:Smad3:Eomes gene
Nodal-Smad2,3 signaling is crucial for induction of Eomes expression as Eomes is absent in Nodal-deficient mice (Brennan et al. 2001). In mouse embryonic stem cells during differentiation towards mesendoderm progenitors, Foxh1 and Smad3 are pre-bound to the Eomes gene (Aragon et al. 2019). Upon Nodal signaling Smad2 is phosphorylated and transits to the nucleus with Smad4 to bind and activate expression of the Eomes gene and other genes such as Gsc (Wang et al. 2017, Aragon et al. 2019). The same process is inferred to occur during generation of mesoderm and endoderm precursors in the primitive streak. In Foxh1 deficient embryos, Eomes remains expressed suggesting that other forkhead factors may act in the activation of Eomes expression (Simon et al. 2017). A TCF-binding element bound by Tcf3 in a Smad2,3 bound enhancer is a also important for proper Eomes expression (Wang et al. 2017).
Literature References
PubMed ID Title Journal Year
27889317 The p53 Family Coordinates Wnt and Nodal Inputs in Mesendodermal Differentiation of Embryonic Stem Cells

Huangfu, D, Li, QV, Zou, Y, Shu, W, Soh, CL, Massagué, J, Wang, Q, Nowotschin, S, Hadjantonakis, AK, Zhang, C, Su, J, Xi, Q, Kim, SY

Cell Stem Cell 2017
28174238 Functional characterisation of cis-regulatory elements governing dynamic Eomes expression in the early mouse embryo

Bikoff, EK, Costello, I, Simon, CS, Hughes, JR, Higgs, DR, Downes, DJ, Telenius, J, Robertson, EJ, Gosden, ME

Development 2017
31582430 Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-β signaling

Tian, L, Macias, MJ, Hu, J, Zou, Y, Shu, W, Massagué, J, Aragón, E, Wang, Q, Hadjantonakis, AK, Su, J, Gomes, T, Agrawal, S, Kaczmarska, Z, Torner, C, Márquez, JA, Ruiz, L, Morgani, SM

Genes Dev 2019
Participants
Input
Output
Orthologous Events
p-2S-SMAD2,3:SMAD4, CTNNB1, and TBPL2 bind FOXH1:SMAD3:EOMES gene (Homo sapiens)
Authored
May, B  (2021-09-23)
Reviewed
Tam, PPL  (2022-05-08)
Probst, S  (2022-07-18)
Salehin, N  (2022-05-08)
Zissel, L  (2022-07-18)
Created
May, B  (2021-09-28)
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