Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory
The histone modification H3K27me3 plays a central role in Polycomb-mediated epigenetic silencing. H3K27me3 recruits and allosterically activates Polycomb Repressive Complex 2 (PRC2), which adds this modification to nearby histones, providing a read/write mechanism for inheritance through DNA replication. However, for some PRC2 targets, a purely histone-based system for epigenetic inheritance may be insufficient. We address this issue at the Polycomb targetFLOWERING LOCUS C (FLC) inArabidopsis thaliana, as a narrow nucleation region of only ~three nucleosomes withinFLC mediates epigenetic state switching and subsequent memory over many cell cycles. To explain the memory ’s unexpected persistence, we introduce a mathematical model incorporating extra protein memory storage elements with positive feedback that persist at the locus through DNA replication, in addition to histone modifications. Our hybrid model explains many features of epigenetic switching/memory atFLC and encapsulates generic mechanisms that may be widely applicable.