Stat6, Nfatc2 (Nfat1), and Nicd1,2 bind the Gata3 gene and cause displacement of repressor complexes (Prc1, Rbpj:NcoR) by activator complexes (Mll1, Rbpj:Nicd1,2)

Stable Identifier
R-MMU-9977960
Type
Reaction [binding]
Species
Mus musculus
Compartment
nucleoplasm
ReviewStatus
5/5
General
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PNG
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Medium
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Stat6, Nfatc2 (Nfat1), and Nicd1,2 bind the Gata3 gene and cause displacement of repressor complexes (Prc1, Rbpj:NcoR) by activator complexes (Mll1, Rbpj:Nicd1,2)
Il4 signaling via Il4ra produces phosphorylated Stat6 dimers (reviewed in Keegan et al. 2021), which enter the nucleus and bind within the transcribed region of the Gata3 gene (Wei et al. 2010, Onodera et al. 2010) and in the proximal and distal promoters of Gata3 (Scheinman and Avni 2009). Binding of phosphorylated Stat6 causes displacement of repressive Prc1 complexes and recruitment of Mll1 complexes (Onodera et al. 2010). The displacement of Prc1 by Mll1 complexes is most pronounced between the proximal and distal promoters of the Gata3 gene and is not evident about 5 kb upstream of the distal promoter (Onodera et al. 2010).
Signaling by the T cell receptor results in increased cytosolic Ca2+, which activates calcineurin to dephosphorylate multiply phosphorylated Nfatc2 (Nfat1), yielding monophosphorylated Nfatc2 (p-S245-Nfatc2) (Scheinman and Avni 2009) that enters the nucleus and binds 3 conserved noncoding sequences, the distal promoter, and the proximal promoter of the Gata3 gene (Scheinman and Avni 2009).
Jagged1 or Jagged2 on antigen presenting cells activates signaling by Notch1 and Notch2 in T cells to enhance expression of Gata3 (Amsen et al. 2004, 2007, Fang et al. 2007). Nicd1 or Nicd2 resulting from Notch signaling binds Rbpj bound to the upstream (distal) promoter of the Gata3 gene, about 10 kb upstream of the proximal promoter (Amsen et al. 2007, Fang et al. 2007). Nicd1,2 causes displacement of Rbpj-bound NCoR corepressors by Maml and coactivators.
Literature References
PubMed ID Title Journal Year
34557875 Recent advances in understanding the role of IL-4 signaling

Keegan, AD, Leonard, WJ, Zhu, J

Fac Rev 2021
17658279 Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

Amsen, D, Antov, A, Jankovic, D, Sher, A, Radtke, F, Souabni, A, Busslinger, M, McCright, B, Gridley, T, Flavell, RA

Immunity 2007
19056736 Transcriptional regulation of GATA3 in T helper cells by the integrated activities of transcription factors downstream of the interleukin-4 receptor and T cell receptor

Scheinman, EJ, Avni, O

J Biol Chem 2009
15137944 Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells

Amsen, D, Blander, JM, Lee, GR, Tanigaki, K, Honjo, T, Flavell, RA

Cell 2004
20620946 Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation

Wei, L, Vahedi, G, Sun, HW, Watford, WT, Takatori, H, Ramos, HL, Takahashi, H, Liang, J, Gutierrez-Cruz, G, Zang, C, Peng, W, O'Shea, JJ, Kanno, Y

Immunity 2010
20956546 STAT6-mediated displacement of polycomb by trithorax complex establishes long-term maintenance of GATA3 expression in T helper type 2 cells

Onodera, A, Yamashita, M, Endo, Y, Kuwahara, M, Tofukuji, S, Hosokawa, H, Kanai, A, Suzuki, Y, Nakayama, T

J Exp Med 2010
17658278 Notch directly regulates Gata3 expression during T helper 2 cell differentiation

Fang, TC, Yashiro-Ohtani, Y, Del Bianco, C, Knoblock, DM, Blacklow, SC, Pear, WS

Immunity 2007
Participants
Input
Output
Orthologous Events
STAT6, NFATC2 (NFAT1), and NICD1,2 bind the GATA3 gene and cause displacement of repressor complexes (PRC1, RBPJ:NCOR) by activator complexes (MLL1, RBPJ:NICD1,2) (Homo sapiens)
Authored
May, B  (2025-12-23)
Reviewed
Barbutti, I  (2026-02-24)
Lord, GM  (2026-02-26)
Created
May, B  (2025-12-27)
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