Competition for H2A.Z between genes and repetitive elements establishes response to anti-viral immune activation

Abstract

Activation of endogenous retroviruses leads to widespread transcriptional reprograming, affecting innate immune activation, metabolic control, and development. We find that the histone variant H2A.Z plays a central role in orchestrating these responses. Stimulating retroviral expression in zebrafish embryos causes H2A.Z to exit developmental gene promoters, which become silent, and to accumulate specifically at primed repetitive elements, which are pre-marked by H3K27ac and H3K9me3. Remarkably, this rewiring is greatly influenced by total H2A.Z abundance, and developmental consequences of retrovirus activation are mitigated by H2A.Z over-expression. Our results uncover mechanisms whereby H2A.Z levels determine sensitivity to retroviral activation, and repetitive elements function as a nuclear sink to dramatically influence total transcriptional output. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/486614v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@275f37org.highwire.dtl.DTLVardef@dc2d9aorg.highwire.dtl.DTLVardef@135f599org.highwire.dtl.DTLVardef@18f290c_HPS_FORMAT_FIGEXP M_FIG C_FIG