Characterization of promoter of the tuberculosis-resistant gene intracellular pathogen resistance 1.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, which most commonly affects the lungs and causes over 1.3 million people die annually. Variation in host genes is known to influence susceptibility to tuberculosis. Expression of the intracellular pathogen resistance 1 (Ipr1) gene could enhance the host resistance to mycobacterium. Here, we analyzed the coding region sequence and promoter of Ipr1 gene of mouse strains C57BL/6 and BALB/c. We found that the coding sequences of Ipr1 gene both in C57BL/6 and in BALB/c mice encode the same protein, while the Ipr1 promoter of BALB/c exists a short deletion and showed a slight of decreased transcriptional activity when compared with C57BL/6. Moreover, the optimal and minimal Ipr1 promoter was identified by luciferase assays using truncated reporter constructs, and the region from -293 to +95 bp showed the highest transcriptional activity and responsible for IFN-γ stimulation. Furthermore, the results showed that IFN-γ activates JAK/STAT and NF-κB signaling pathways to induce Ipr1 expression, and the signal transducer and activator of transcription 1 (Stat1) are critical for IFN-γ-induced Ipr1 expression, because overexpression of Stat1 promotes Ipr1 transcription, but knockdown of Stat1 reduced Ipr1 expression. Collectively, for the first time, our study characterizes Ipr1 promoter and investigates the positive and negative regulation of Ipr1 expression, providing basic data for application of Ipr1 in animal breeding.