Polycomb proteins translate histone methylation to chromatin folding

Abstract

Epigenetic repression often involves covalent histone modifications. Yet, how the presence of a histone mark translates into changes in chromatin structure that ultimately benefit the repression is largely unclear. Polycomb group proteins comprise a family of evolutionarily conserved epigenetic repressors. They act as multi-subunit complexes one of which trimethylates histone H3 at Lysine 27 (H3K27). Here we describe a novel Monte Carlo - Molecular Dynamics simulation framework, which we employed to discover that stochastic interaction of the Polycomb Repressive Complex 1 (PRC1) with tri-methylated H3K27 is sufficient to fold the methylated chromatin. Unexpectedly, such chromatin folding leads to spatial clustering of the DNA elements bound by PRC1.