Gata3, Chd4, Ep300, Nfatc2 (Nfat1), Fos:Jun (AP-1), Klf13, Maf, Yy1, Ets1, Pou2f1 (Oct1), Pou2f2 (Oct2), Batf, Satb1, Irf4, Smarca4, and Stat6 positively regulate expression of Il4

Stable Identifier
R-MMU-9978102
Type
Reaction [omitted]
Species
Mus musculus
Compartment
nucleoplasm
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Gata3, Chd4, Ep300, Nfatc2 (Nfat1), Fos:Jun (AP-1), Klf13, Maf, Yy1, Ets1, Pou2f1 (Oct1), Pou2f2 (Oct2), Batf, Satb1, Irf4, Smarca4, and Stat6 positively regulate expression of Il4
Il4 signaling enhances expression of Gata3, which binds with Chd4 and Ep300 to the second intron of the Il4 gene (Zheng and Flavell 1997, Sasaki et al. 2013). Ep300 recruited by Gata3 and Chd4 causes the acetylation of histones in the region of Il4 and Il13 (Hosokawa et al. 2013). Nfatc2 (Nfat1) activated by T cell receptor signaling binds with Fos:Jun (AP-1) to the promoter of the Il4 gene (Szabo et al. 1993, Rooney et al. 1995, Takemoto et al. 1997). Klf13 binds a CACCC element in the promoter of the Il4 gene and interacts with Maf bound to the Il4 promoter (Kwon et al. 2014).
Gata3, Chd4, Ep300, Nfatc2, Fos:Jun, Klf13, and Maf activate transcription of Il4 (Szabo et al. 1993, Rooney et al. 1995, Zheng and Flavell 1997, Takemoto et al. 1997, Hosokawa et al. 2013, Sasaki et al. 2013, Kwon et al. 2014). Gata3, Yy1, Ets1, Pou2f1 (Oct1), Pou2f2 (Oct2), Batf, Satb1, Irf4, Smarca4, and Stat6 bound to the locus control region (LCR) also enhance expression. Continued activation by Gata3 is required for expression of Il4 in memory Th2 cells (Sasaki et al. 2013).
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
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
23824597 Genome-Wide Gene Expression Profiling Revealed a Critical Role for GATA3 in the Maintenance of the Th2 Cell Identity

Sasaki, T, Onodera, A, Hosokawa, H, Watanabe, Y, Horiuchi, S, Yamashita, J, Tanaka, H, Ogawa, Y, Suzuki, Y, Nakayama, T

PLoS One 2013
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
This event is regulated
Positively by
Regulator
Gata3:Yy1:Ets1:Pou2f1:Pou2f2:Batf:Irf4:Satb1:Smarca4:p-Y641-Stat6:Rad50 gene [nucleoplasm] (Mus musculus)
Regulator
Gata3:Chd4:Ep300:p-S245-Nfatc2:Fos:Jun:Klf13:Maf:Il4 gene [nucleoplasm] (Mus musculus)
Active Unit
Fos:Jun [nucleoplasm]
Gata3 [nucleoplasm]
Klf13 [nucleoplasm]
Maf [nucleoplasm]
p-S245-Nfatc2 [nucleoplasm]
Orthologous Events
GATA3, CHD4, EP300, NFATC2 (NFAT1), FOS:JUN (AP-1), KLF13, MAF, YY1, ETS1, POU2F1 (OCT1), POU2F2 (OCT2), BATF, SATB1, IRF4, SMARCA4, and STAT6 positively regulate expression of IL4 (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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