ISRE

ISRE is the acronym for IFN-stimulated response elements. The ISRE element serves as a binding site for a family of transcription factors called IFN regulatory factors (IRFs) (Heim MH 1999).

Type I and type II interferons induce IFN-stimulated gene (ISG) expression through Janus kinase (JAK)-dependent phosphorylation of Signal Transducer and Activator of Transcription (STAT) STAT1 and STAT2. The evolutionarily highly conserved interferon-stimulated genes (Levraud JP et al. 2019) are the effectors of interferon (IFN) actions and play an important role in innate immune defense against microbial infections (Green R et al. 2018).

STAT1 homodimers, known as gamma-activated factor (GAF), activate transcription in response to all types of interferons by directly binding GEne containing the one IFN-II activation site.

The association of interferon regulatory factor 9 (IRF-9) with STAT1-STAT2 heterodimers (known as interferon-stimulated gene factor 3 - ISGF3) or with STAT2 homodimers(STAT2/IRF9) in response to IFN-I directs these complexes to a specific group of target genes containing the interferon-stimulated response element (ISRE) to which they can bind (Michalska A et al. 2018).

Studies with knockout mice showed that IRF-4 plays a critical role in controlling the activation and homeostasis of immune responses and is crucial for the maturation of B cells. IRF-8\ICSBP is essential for myeloid cell differentiation into mature macrophages.

To date, nine cellular IFN regulatory factors have been identified. Some of the IRFs, such as IRF-1, IRF-2, IRF-3, and IRF-7, bind directly to ISRE elements, whereas others, such as IRF-4 and IRF-8, bind only indirectly. Thus, IRF8/ICSBP can associate with either IRF-1 or IRF-2 and form heterocomplexes that then bind to DNA. These protein-protein interactions are mediated by a conserved domain. This domain is referred to as the IRF association domain (IAD). This IAD motif can be detected in all seven IRFs except IRF-1 and IRF-2.

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3. Levraud JP et al (2019) IFN-stimulated genes in zebrafish and humans Define an Ancient Arsenal of Antiviral Immunity. J Immunol 203:3361-3373.
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