Epigenetic signals that direct cell type-specific interferon beta response in mouse cells

Area of Science:

• Immunology
• Epigenetics
• Molecular Biology

Background:

• Type I interferon (IFN) triggers antiviral responses by activating hundreds of interferon-stimulated genes (ISGs) through the JAK-STAT pathway.
• ISG expression profiles vary significantly between cell types, but the underlying epigenetic mechanisms remain poorly understood.

Purpose of the Study:

• To investigate the relationship between epigenetic features and cell type-specific ISG profiles.
• To understand how chromatin states influence the antiviral response to IFN.

Main Methods:

• Mapping of ISGs, STAT1/2 transcription factor binding sites, chromatin accessibility, and specific histone modifications (H3K4me1, H3K27ac, H3K27me3) in mouse cells.
• Analysis of these features before and after IFNβ treatment using chromatin co-accessibility analysis.

Main Results:

• A significant portion of ISGs and STAT-binding sites were cell type-specific, with STAT1/2 complex binding at promoters being a key driver.
• STAT1/2 binding to enhancers also induced ISGs, dependent on chromatin context.
• STAT1/2 binding correlated positively with open chromatin and pre-existing H3K4me1 and H3K27ac marks, while H3K27me3 showed an inhibitory effect.

Conclusions:

• Pre-existing epigenetic features, including specific histone marks and chromatin accessibility, act as a regulatory layer controlling cell type-specific antiviral responses.
• These chromatin states prime cells for differential ISG induction upon IFN stimulation.