Interferon-stimulated response element (ISRE)

Interferon-stimulated response elements (ISREs) are essential cis-regulatory DNA sequences located within the promoter and enhancer regions of interferon-stimulated genes (ISGs). These elements serve as the primary binding sites for Interferon Regulatory Factors (IRFs), such as IRF1, IRF3, and IRF7, as well as the ISGF3 heterotrimeric complex (STAT1-STAT2-IRF9), which are activated downstream of type I and type III interferon signaling pathways. Upon activation and translocation to the nucleus, these transcription factors bind to the ISRE consensus sequence (typically AGTTTNCNTTTC) to drive the expression of hundreds of genes that establish a cellular antiviral state and modulate innate and adaptive immune responses. While the DNA elements themselves are not traditional targets for small molecule binding, they represent the critical functional endpoint for therapeutic agents such as exogenous interferons, JAK inhibitors, and STING agonists. Dysregulation of ISRE-mediated gene expression is a central feature of various pathologies, including chronic viral infections, malignancies, and autoimmune 'interferonopathies' like systemic lupus erythematosus and Aicardi-Goutières syndrome.

Other names

IRF-responsive elementIRF-binding elementIRF-EInterferon-stimulated gene promoter elementCis-acting interferon-responsive elementPRDI-III elements

Recruitment and binding of Interferon Regulatory Factors (IRFs) and the ISGF3 complex (STAT1-STAT2-IRF9) to initiate the transcription of antiviral and immunomodulatory genes.