Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory

eLife

Pawel Mikulski¹  Caroline Dean¹  Cecilia Lövkvist²  Matthew Hartley²  Martin Howard²  Svenja Reeck³ 

[1] Cell and Developmental Biology, John Innes Centre, Norwich Research Park, United Kingdom;Computational and Systems Biology, John Innes Centre, Norwich Research Park, United Kingdom;Computational and Systems Biology, John Innes Centre, Norwich Research Park, United Kingdom;Cell and Developmental Biology, John Innes Centre, Norwich Research Park, United Kingdom;

关键词: FLC;    epigenetics;    mathematical modelling;    PRC2;    polycomb;    H3K27me3;    A. thaliana;   

DOI  :  10.7554/eLife.66454

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 target FLOWERING LOCUS C (FLC) in Arabidopsis thaliana, as a narrow nucleation region of only ~three nucleosomes within FLC 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 at FLC and encapsulates generic mechanisms that may be widely applicable.

【 授权许可】

CC BY