BRD9 is a Druggable Component of Interferon-Stimulated Gene Expression and Antiviral Activity

ABSTRACT: Interferon (IFN) induction of IFN-stimulated genes (ISGs) creates a formidable protective antiviral state. However, loss of appropriate control mechanisms can result in constitutive pathogenic ISG upregulation. Here, we used genome-scale loss-of-function screening to establish genes critical for IFN-induced transcription, identifying all expected members of the JAK-STAT signaling pathway and a previously unappreciated epigenetic reader, bromodomain-containing protein 9 (BRD9), the defining subunit of non-canonical BAF (ncBAF) chromatin remodeling complexes. Genetic knock-out or small-molecule mediated degradation of BRD9 limits IFN-induced expression of a subset of ISGs in multiple cell-types, and prevents IFN from exerting full antiviral activity against several RNA and DNA viruses, inclu

SUBMITTER: Jacob Börold 

PROVIDER: S-SCDT-EMBOR-2021-52823-T | biostudies-other |

REPOSITORIES: biostudies-other