Characterization of promoter of the tuberculosis-resistant gene intracellular pathogen resistance 1
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ORIGINAL ARTICLE
Characterization of promoter of the tuberculosis-resistant gene intracellular pathogen resistance 1 Yongyan Wu1,2 • Fayang Liu1,2 • Yan Zhang1,2 • Yongsheng Wang1,2 Zekun Guo1,2 • Yong Zhang1,2
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Published online: 21 November 2015 Ó Springer Science+Business Media New York 2015
Abstract 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-c stimulation. Furthermore, the results showed that IFN-c activates JAK/STAT and NF-jB signaling pathways to induce Ipr1 expression, and the signal transducer and activator of transcription 1 (Stat1) are critical for IFN-c-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 Yongyan Wu and Fayang Liu have contributed equally to this work. & Yong Zhang [email protected] 1
College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China
2
Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, 3 Taicheng Road, Yangling 712100, Shaanxi, China
investigates the positive and negative regulation of Ipr1 expression, providing basic data for application of Ipr1 in animal breeding. Keywords Ipr1 Gene promoter Stat1 IFN-c Mycobacterium
Introduction Tuberculosis is one of the biggest health challenges worldwide, and one-third of the human population is infected with Mycobacterium tuberculosis and more than 1 million die annually [1]. Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, is hard to be eradicated from infected cells. However, only 10 % of latent infections progress to active tuberculosis; most people infected with MTB remain asymptomatic, which indicates the importance of host immune defense against mycobacterial infection [2, 3]. A large number of studies on MTB pathogenesis and immune response to MTB infection have been carried on using inbred laboratory mice, because humans and mice are similar in the main features of the innate and adaptive immune responses to mycobacteria [4]. As in humans, the results of different strains of mice infecte
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