EOMES, TBXT (T BRACHYURY), GATA6, and SMAD2,3 bind the FOXA2 gene

Stable Identifier
Reaction [binding]
Homo sapiens
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In mouse embryos, Foxa2 is expressed in the posterior epiblast and then confined to the anterior primitive streak in progenitors of axial mesoderm and endoderm (Burtscher and Lickert 2009). The high level of NODAL signaling in the anterior primitive streak (inferred from mouse embryos) activates FOXA2 through the phosphorylation of SMAD2 and SMAD3 proteins that, together with the SMAD4 coregulator, bind the promoter of the FOXA2 gene (inferred from human pluripotent stem cells in Brown et al. 2011, Teo et al. 2011, Jiang et al. 2015). EOMES and TBXT (T, BRACHYURY) that are expressed early in the primitive streak also bind and activate the FOXA2 gene (inferred from human pluripotent stem cells in Teo et al. 2011, Chia et al. 2019, inferred from human embryonic stem cells in Faial et al. 2015, also inferred from mouse homologs). GATA6, which is also activated by NODAL signaling, binds the FOXA2 promoter and activates expression (Chia et al. 2019). The DEANR1 lncRNA is divergently transcribed from a region upstream of the FOXA2 gene and enhances association of SMAD2,3 with the FOXA2 promoter (Jiang et al. 2015). Activity of DIGIT, a long non-coding RNA transcribed from between the enhancer and the GSC coding region, enhances the transcription of FOXA2 (Daneshvar et al. 2016)
Literature References
PubMed ID Title Journal Year
30629940 GATA6 Cooperates with EOMES/SMAD2/3 to Deploy the Gene Regulatory Network Governing Human Definitive Endoderm and Pancreas Formation

Dunn, NR, Garcia-Bernardo, J, Chia, CY, Hattersley, AT, Madrigal, P, Vallier, L, Chhatriwala, M, Denil, SLIJ, El-Khairi, R, Shepherd, MH, Martinez, I

Stem Cell Reports 2019
21630377 Activin/Nodal signaling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors

Dunn, NR, Lim, B, Cho, CH, Vallier, L, Pedersen, R, Hannan, N, Teo, A, Vardy, L, Brown, S, Trotter, M, Pauklin, S

Stem Cells 2011
25843708 The lncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression

Zhang, K, Zhang, Y, Liu, R, Jiang, W, Liu, Y

Cell Rep 2015
26015544 Brachyury and SMAD signalling collaboratively orchestrate distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells

Smith, JC, Diamanti, E, Pedersen, RA, Trotter, MW, Mascetti, VL, Faial, T, Gentsch, GE, Ortmann, D, Bernardo, AS, Mendjan, S

Development 2015
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
27705785 DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control Definitive Endoderm Differentiation of Embryonic Stem Cells

York, SR, Macklin, JA, Tan, B, Abualteen, A, Sigova, AA, Kim, BM, Daneshvar, K, Mullen, AC, Tremblay, KD, Zhou, C, Pondick, JV, Choi, MY, Mager, J, Marcho, C

Cell Rep 2016
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