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DNA-binding of IRF3, IRF5 and IRF7 transcription factors

ABSTRACT: The Interferon Regulatory Factors (IRFs) are essential regulators of the innate immune response to viruses. IRFs 3, 5, and 7 drive type-1-interferon and cytokine production in a cell-type and stimulus-specific manner, suggesting regulatory complexity. IRFs 3, 5 and 7 bind DNA as phosphorylation-activated dimers and are classically described as binding a doublet of the canonical IRF binding site: 5'-AANNGAAA-3’. IRF3/5/7 have both common and distinct gene targets and the simple canonical motif does not capture the regulatory complexity of IRF-dependent gene expression. Previous studies, both low and high throughput, have refined our understanding of IRF regulation, yet a systematic comparison of DNA binding preferences for active, dimeric IRF complexes has not been performed. To address this, we designed an IRF-specific, custom protein-binding microarray (PBM) that includes synthetic IRF binding sites as well as type-1-interferon and cytokine promoters. Using constitutively active, phosphomimetic IRF3, 5 and 7 dimers, we find key DNA binding differences for these factors with implications for IRF-dependent gene regulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109117 | GEO | 2018/01/12

SECONDARY ACCESSION(S): PRJNA429664

REPOSITORIES: GEO

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