Abstract
Interferon-stimulated genes (ISGs) play an important role in antiviral innate immune responses. Although many ISGs have been identified in mammals, researchers commonly recognize that many more ISGs are yet to be discovered. Current information is still very limited particularly for the systematic identification of type III ISGs. Similarly, current research on ISGs in birds is still in its infancy. The aim of this study was to systematically identify chicken type I (IFN-α), II (IFN-γ) and III (IFN-λ) ISGs and analyze their respective response elements. RNA sequencing (RNA-Seq) was employed to identify those genes with up-regulated expression following chicken IFN-α, IFN-γ and IFN-λ treatment. Two hundred and five type I ISGs, 299 type II ISGs, and 421 type III ISGs were identified in the chicken. We further searched for IFN-stimulated response elements (ISRE) and gamma-activated sequences (GAS) elements in the promoters region of ISGs. The GAS elements were common in the promoter of type II ISGs and were even detected in type I and III ISGs. However, ISRE were not commonly found in the promoters of chicken ISGs. Furthermore, we demonstrated that ISRE in chicken cells were significantly activated by IFN-α or IFN-λ treatment, and expectedly, that GAS elements were also significantly activated by IFN-γ treatment. Interestingly, we also found that GAS elements were significantly activated by IFN-λ. Our study provides a systematic library of ISGs in the chicken together with preliminary information about the transcriptional regulation of the identified ISGs.
Highlights
Based on sequence homology and receptor specificity, interferons (IFNs) are divided into three types, i.e. type I, II and III [1]
Phosphorylated STAT1 and STAT2 form a heterodimer that translocates to the nucleus to form the heterotrimeric transcription factor complex consisting of IFN-stimulated genes factor 3 (ISGF3) with IRF-9, thereby inducing hundreds of Interferon-stimulated genes (ISGs) after binding the IFN-stimulated response elements (ISREs)
Activation by type II IFN only involves the dimerization of phosphorylated STAT1 to form γ-interferon activation factor (GAF) that translocates to the nucleus and binds to gammaactivated sequences (GAS) of response genes [7]
Summary
Based on sequence homology and receptor specificity, interferons (IFNs) are divided into three types, i.e. type I, II and III [1]. In the canonical pathway for generating ISGs, IFN-induced signaling initially results in the phosphorylation of receptor-associated tyrosine kinases of the Janus kinase (JAK) family of proteins, which phosphorylate the signal transducer and activator of. Phosphorylated STAT1 and STAT2 (during type I or III IFN stimulation) form a heterodimer that translocates to the nucleus to form the heterotrimeric transcription factor complex consisting of IFN-stimulated genes factor 3 (ISGF3) with IRF-9, thereby inducing hundreds of ISGs after binding the IFN-stimulated response elements (ISREs). Activation by type II IFN only involves the dimerization of phosphorylated STAT1 to form γ-interferon activation factor (GAF) that translocates to the nucleus and binds to gammaactivated sequences (GAS) of response genes [7]
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