Characterization and analysis of the proximal Janus kinase 3 promoter

Aringer, Martin and Hofmann, Sigrun R. and Frucht, David M. and Chen, Min and Centola, Michael and Morinobu, Akio and Visconti, Roberta and Kastner, Daniel L. and Smolen, Josef S. and O'Shea, John J. (2003) Characterization and analysis of the proximal Janus kinase 3 promoter. The Journal of Immunology, 170 (12). pp. 6057-6064. ISSN 1550-6606

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Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase essential for signaling via cytokine receptors that comprise the common ϒ-chain (ϒc), i.e., the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is preferentially expressed in hemopoietic cells and is up-regulated upon cell differentiation and activation. Despite the importance of Jak3 in lymphoid development and immune function, the mechanisms that govern its expression have not been defined. To gain insight into this issue, we set out to characterize the Jak3 promoter. The 5'-untranslated region of the Jak3 gene is interrupted by a 3515-bp intron. Upstream of this intron and the transcription initiation site, we identified an ~1-kb segment that exhibited lymphoid-specific promoter activity and was responsive to TCR signals. Truncation of this fragment revealed that core promoter activity resided in a 267-bp fragment that contains putative Sp-1, AP-1, Ets, Stat, and other binding sites. Mutation of the AP-1 sites significantly diminished, whereas mutation of the Ets sites abolished, the inducibility of the promoter construct. Chromatin immunoprecipitation assays showed that histone acetylation correlates with mRNA expression and that Ets-1/2 binds this region. Thus, transcription factors that bind these sites, especially Ets family members, are likely to be important regulators of Jak3 expression. The Journal of Immunology, 2003, 170: 6057–6064.

Item Type: Article
Subjects: 500 Scienze naturali e Matematica
500 Scienze naturali e Matematica > 570 Scienze della vita; Biologia
Depositing User: Dr Roberta Visconti
Date Deposited: 11 Jan 2017 14:54
Last Modified: 11 Jan 2017 14:54

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