ArticleProceedings of the National Academy of Sciences of the United States of America1993
Molecular dissection of the mouse interleukin-4 promoter.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 57 citations in OpenAlex.
- Association ofMedicina (Kaunas, Lithuania) · 2020Article
- The receptor NLRP3 is a transcriptional regulator of TH2 differentiation.Nature immunology · 2015Article
- Early growth response protein-1 (Egr-1) is preferentially expressed in T helper type 2 (Th2) cells and is involved in acute transcription of the Th2 cytokine interleukin-4.The Journal of biological chemistry · 2010Article
- Mina, an Il4 repressor, controls T helper type 2 bias.Nature immunology · 2009Article
- Yin-Yang 1 regulates effector cytokine gene expression and T(H)2 immune responses.The Journal of allergy and clinical immunology · 2008Article
- Phosphoinositide-dependent kinase 1 targets protein kinase A in a pathway that regulates interleukin 4.The Journal of experimental medicine · 2006Article
- Characterization of a novel negative regulatory element in the human interleukin 4 promoter.Leukemia · 2000Article
- Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation.The EMBO journal · 1999Article
- Impaired interleukin 4 signaling in T helper type 1 cells.The Journal of experimental medicine · 1998Article
- Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells.Molecular and cellular biology · 1997Article
- Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells.The Journal of experimental medicine · 1997Article
- HMG I(Y) interferes with the DNA binding of NF-AT factors and the induction of the interleukin 4 promoter in T cells.Proceedings of the National Academy of Sciences of the United States of America · 1996Article
- Nuclear factor of activated T cells is associated with a mast cell interleukin 4 transcription complex.Molecular and cellular biology · 1996Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the molecular mechanisms regulating the expression of interleukin 4 (IL-4) may shed light on the differentiation of lymphokine-producing phenotypes of CD4+ T cells. We have identified two DNA segments that are necessary for full phorbol 12-myristate 13-acetate (PMA)-induced activity of the IL-4 promoter region in the thymoma cell line EL4. Through deletion and mutation analyses, one of these segments (-57 through -47) was shown to be indispensable for promoter function. We designated this sequence consensus sequence 1 (CS1), as it shares homology with a sequence (ATTTTCCNNTG) that appears five times in the proximal 302-base-pair (bp) region 5' of the gene. We examined CS1 in further detail, as well as a second consensus sequence, CS2, located at nucleotides -75 through -65; both are within a minimal 83-bp construct that expresses full promoter activity. CS1- and CS2-spanning oligonucleotides bound apparently distinct PMA-inducible, sequence-specific factors in mobility-shift assays. Multimer constructs linking CS1- or CS2-spanning oligonucleotides to a heterologous promotor revealed that the CS1 construct had the greater enhancer activity in EL4 cells. Mutating the CS1 sequence within the context of the 302-bp promoter abolished all activity of the promoter, while mutating the CS2 sequence alone had little effect. Furthermore, a CS1 multimer could drive a heterologous promoter in an IL-4-producing [helper T-cell type 2 (TH2-type)] T-cell clone but not in a non-IL-4-producing (TH1-type) clone, suggesting a mechanism by which IL-4 production could be differentially regulated in TH subsets.
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