Janus kinase 3 (Jak3) is a nonreceptor tyrosine kinase essential for signaling 
via cytokine receptors that comprise the common gamma-chain (gammac), 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 
approximately 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.