A genetic variant controls interferon-β gene expression in human myeloid cells by preventing C/EBP-β binding on a conserved enhancer

Interferon beta is a central cytokine in the antiviral response and the immunogenicity of cancer therapies. In monocytes, its expression is modulated by a 60 kb downstream eQTL. We found that this eQTL disrupts binding of the C/EBP-β transcription factor to an enhancer interacting with the IFNB1 promoter. This enhancer, that we have called FIRE for Far IFNB1 Regulatory Enhancer, is conserved in murine myeloid cells, where its looping to Ifnb1 is increased in a genetic model of Ifnb1 deregulation. Precisely, we show that in murine myeloid cells, the TRIM33 chromatin reader partially co-localizes with CTCF and cohesin on the chromatin, and knocking out Trim33 reinforces a loop between Ifnb1 and FIRE. In order to identify CTCF and cohesin peaks in murine myeloid cells, we performed ChIP-seq targeting CTCF and RAD21 in the RAW264,7 cell line. Input were used as controls.