Model of EBV latency promoter epigenetic remodeling by GC cytokine driven JAK/STAT signaling.

Abstract

Cytokines secreted by germinal center FDC and Tfh cells trigger JAK/STAT signaling to drive STAT homodimer or heterodimer nuclear translocation. STAT dimers bind to the C promoter together with a co-repressor to increase levels of repressive 5-methylcytosine (5-mC), H3K9me2/3 and H2AK119Ub epigenetic marks, while decreasing activating H3K27Ac marks. C promoter inactivation decreases latency III EBNA expression. By contrast, STAT dimers bind to the LMP1 promoter together with a co-activator to drive epigenetic remodeling to increase levels of LMP1 promoter H3K27Ac and to decrease levels of H2AK119Ub, which supports LMP1 expression despite concurrently increased 5mC levels. By contrast, GC cytokines increase the abundances of LMP2 promoter repressive H2AK119Ub, H3K9me3 and 5mC marks to downmodulate LMP2 expression from levels observed in latency III. (BioRender was used to create the schematic models).</p