Gata3, Chd4, Ep300, p-S243-Nfatc2 (p-S243-Nfat1), Fos:Jun (AP-1), Klf13, and Maf bind the Il4 gene

Stable Identifier
R-MMU-9978110
Type
Reaction [binding]
Species
Mus musculus
Compartment
nucleoplasm
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Gata3, Chd4, Ep300, p-S243-Nfatc2 (p-S243-Nfat1), Fos:Jun (AP-1), Klf13, and Maf bind the Il4 gene
Expression of Gata3, the master regulator of Th2 differentiation, is activated by Il4 signaling. Gata3, Chd4, and Ep300 then bind the Il4 gene (Zheng and Flavell 1997, Horiuchi et al. 2011, Wei et al. 2011, Hosokawa et al. 2013). Gata3, Chd4, and Ep300 bind within intron 2 of the Il4 gene (Hosokawa et al. 2013).
Translocation of Nfatc2 (Nfat1) to the nucleus is activated by T cell receptor signaling via Ca2+, which activates Calcineurin-catalyzed dephosphorylation and nuclear entry of Nfatc2. Nfatc2 binds with Jun:Fos (AP-1) to purine-rich elements in the promoter of the Il4 gene (Szabo et al. 1993, Rooney et al. 1995, Takemoto et al. 1997).
In mice, the Il4 and Il13 genes are located in the same gene cluster on chromosome 11. Gata3 and Nfatc2 (Nfat1) interact with each other and bind within the Il4 and Il13 region to form a chromatin hub (inferred from human homologs in Yao et al. 2012).
In Th2 cells obtained in vivo or differentiated in vitro, Klf13 binds a CACCC element at -338 bp in the Il4 promoter (Kwon et al. 2014) and interacts with Maf bound to two MARE elements in the Il4 promoter to enhance transcription (Ho et al. 1996, Kwon et al. 2014).
Literature References
PubMed ID Title Journal Year
8336717 Identification of cis-acting regulatory elements controlling interleukin-4 gene expression in T cells: roles for NF-Y and NF-ATc

Szabo, SJ, Gold, JS, Murphy, TL, Murphy, KM

Mol Cell Biol 1993
9310836 Four P-like elements are required for optimal transcription of the mouse IL-4 gene: involvement of a distinct set of nuclear factor of activated T cells and activator protein-1 family proteins

Takemoto, N, Koyano-Nakagawa, N, Arai, N, Arai, K, Yokota, T

Int Immunol 1997
23471993 Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity

Hosokawa, H, Tanaka, T, Suzuki, Y, Iwamura, C, Ohkubo, S, Endoh, K, Kato, M, Endo, Y, Onodera, A, Tumes, DJ, Kanai, A, Sugano, S, Nakayama, T

Proc Natl Acad Sci U S A 2013
24821970 KLF13 cooperates with c-Maf to regulate IL-4 expression in CD4+ T cells

Kwon, SJ, Crespo-Barreto, J, Zhang, W, Wang, T, Kim, DS, Krensky, A, Clayberger, C

J Immunol 2014
21536806 Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3

Horiuchi, S, Onodera, A, Hosokawa, H, Watanabe, Y, Tanaka, T, Sugano, S, Suzuki, Y, Nakayama, T

J Immunol 2011
9160750 The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells

Zheng, W, Flavell, RA

Cell 1997
21867929 Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types

Wei, G, Abraham, BJ, Yagi, R, Jothi, R, Cui, K, Sharma, S, Narlikar, L, Northrup, DL, Tang, Q, Paul, WE, Zhu, J, Zhao, K

Immunity 2011
7749982 Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene

Rooney, JW, Hoey, T, Glimcher, LH

Immunity 1995
8674125 The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4

Ho, IC, Hodge, MR, Rooney, JW, Glimcher, LH

Cell 1996
Participants
Input
Output
Orthologous Events
GATA3, CHD4, EP300, NFATC2 (NFAT1), FOS:JUN (AP-1), KLF13, and MAF bind the IL4 gene (Homo sapiens)
Authored
May, B  (2025-12-27)
Reviewed
Barbutti, I  (2026-02-24)
Lord, GM  (2026-02-26)
May, B  (2026-02-28)
Created
May, B  (2025-12-27)
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