p-2S-SMAD2,3:TRIM33, p-2S-SMAD2,3:SMAD4, CTNNB1, EOMES, and TBPL2 bind FOXH1:MIXL1 gene

Stable Identifier
R-HSA-9756724
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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p-2S-SMAD2,3:TRIM33, p-2S-SMAD2,3:SMAD4, CTNNB1, EOMES, and TBPL2 bind FOXH1:MIXL1 gene
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In differentiating human embryonic stem cells (ESCs), beta-catenin (CTNNB1):LEF1, SMAD2,3, and OCT4 bind to an upstream enhancer region (Estarás 2015, Funa 2015) and both SMAD2 and FOXH1 bind to the immediate promoter region of MIXL1 to mediate MIXL1 expression driven by WNT and NODAL signaling. CTNNB1 from WNT signaling binds the promoter and interacts directly with SMAD proteins (Funa et al. 2015). Knockdown of CTNNB1, SMAD2, or OCT4 results in reduced MIXL1 expression (Funa et al. 2015). EOMES binds the enhancer and promoter regions of the MIXL1 gene and is important for transcriptional activation (Teo et al. 2011, and inferred from mouse embryos). The basal transcription factor TBPL2 (TRF3) also binds the promoter of the MIXL1 gene (Liang et al. 2020). NODAL causes phosphorylation of SMAD2 and SMAD3 which then complex with SMAD4 and transit to the nucleus. Phosphorylated SMAD2 and SMAD3 are also present in complexes with TRIM33 in the nucleus (inferred from mouse homologs). SMAD2,3:TRIM33 complexes bind methylated histone H3 lysine-9 and acetylated histone H3 lysine-18 to open chromatin at the MIXL1 promoter (inferred from mouse homologs). SMAD2,3:SMAD4 also binds the MIXL1 promoter (inferred from mouse homologs).
Literature References
PubMed ID Title Journal Year
25936800 SMADs and YAP compete to control elongation of β-catenin:LEF-1-recruited RNAPII during hESC differentiation

Jones, KA, Benner, C, Estarás, C

Mol Cell 2015
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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p-2S-Smad2,3:Trim33 and p-2S-Smad2,3LSmad4 bind Foxh1:Mixl1 gene (Mus musculus)
Authored
May, B  (2021-10-16)
Reviewed
Tam, PPL  (2022-05-08)
Probst, S  (2022-07-18)
Salehin, N  (2022-05-08)
Zissel, L  (2022-07-18)
Created
May, B  (2021-10-18)
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