Epigenetic and transcriptional control of interferon-β

• Published in: The Journal of experimental medicine Vol. 218; no. 9
• Main Authors: Daman, Andrew W., Josefowicz, Steven Z.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 06.09.2021
• Subjects: CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - metabolism; DNA Methylation; Enhancer Elements, Genetic; Epigenesis, Genetic; Gene Expression Regulation; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - physiology; Humans; Infectious Disease and Host Defense; Influenza A Virus, H5N1 Subtype - pathogenicity; Innate Immunity and Inflammation; Interferon-beta - genetics; Interferon-beta - metabolism; Promoter Regions, Genetic; SARS-CoV-2 - pathogenicity; Transcription, Genetic; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Viewpoint
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20210039

The three classes of interferons (IFNs) share the ability to inhibit viral replication, activating cell transcriptional programs that regulate both innate and adaptive responses to viral and intracellular bacterial challenge. Due to their unique potency in regulating viral replication, and their association with numerous autoimmune diseases, the tightly orchestrated transcriptional regulation of IFNs has long been a subject of intense investigation. The protective role of early robust IFN responses in the context of infection with SARS-CoV-2 has further underscored the relevance of these pathways. In this viewpoint, rather than focusing on the downstream effects of IFN signaling (which have been extensively reviewed elsewhere), we will summarize the historical and current understanding of the stepwise assembly and function of factors that regulate IFNβ enhancer activity (the “enhanceosome”) and highlight opportunities for deeper understanding of the transcriptional control of the ifnb gene.