p-2S-Smad2,3:Trim33 and p-2S-Smad2,3LSmad4 bind Foxh1:Mixl1 gene

Stable Identifier
R-MMU-9756720
Type
Reaction [binding]
Species
Mus musculus
Compartment
nucleoplasm
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
p-2S-Smad2,3:Trim33 and p-2S-Smad2,3LSmad4 bind Foxh1:Mixl1 gene
During formation of the primitive streak Foxh1 and Nodal-induced Smad2,3 induce Mixl1 expression (Hart et al. 2005). Nodal causes phosphorylation of Smad2 and Smad3 which then complex with Smad4 and transit to the nucleus. Smad2,3 bind regulatory regions of the Mixl1 gene (Teo et al. 2011, Wang et al. 2017). In the presence of Gsc, which binds the Mixl1 promoter, Foxh1 negatively regulates Mixl1 (Izzi et al. 2007). Eomes also binds regulatory regions of the Mixl1 gene and is important for its activation (Teo et al. 2011, Tosic et al. 2019). Phosphorylated Smad2 and Smad3 are also present in complexes with Trim33 in the nucleus (Xi et al. 2011). Smad2,3:Trim33 complexes bind methylated histone H3 lysine-9 and acetylated histone H3 lysine-18 and may open chromatin at the Mixl1 promoter (Xi et al. 2011).
Literature References
PubMed ID Title Journal Year
31792383 Eomes and Brachyury control pluripotency exit and germ-layer segregation by changing the chromatin state

Köttgen, M, Barg, M, Kim, GJ, Pavlovic, M, Hein, L, Hofherr, A, Mersiowsky, SL, Probst, S, Tosic, J, Arnold, SJ, Schröder, CM

Nat Cell Biol 2019
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
17568773 Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early mouse development

Wrana, JL, Izzi, L, Labbé, E, Zakin, L, Silvestri, C, Attisano, L, von Both, I

EMBO J 2007
33199445 Spatiotemporal sequence of mesoderm and endoderm lineage segregation during mouse gastrulation

Grün, D, Schwan, C, Probst, S, Tosic, J, Arnold, SJ, Sagar, S

Development 2021
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
15982639 Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and FoxH1

Hart, AH, Wong, M, Robb, L, Parker, K, Willson, TA

Biochem Biophys Res Commun 2005
22196728 A poised chromatin platform for TGF-β access to master regulators

Liu, JX, Zaromytidou, AI, Chow-Tsang, LF, Mark, W, Kaartinen, V, Barlas, A, Massagué, J, Manova-Todorova, K, Wang, Z, Studer, L, Zhang, XH, Xi, Q, Patel, DJ, Kim, H

Cell 2011
Participants
Input
Output
Orthologous Events
p-2S-SMAD2,3:TRIM33, p-2S-SMAD2,3:SMAD4, CTNNB1, EOMES, and TBPL2 bind FOXH1:MIXL1 gene (Homo sapiens)
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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