Drawing on disorder: How viruses use histone mimicry to their advantage

Tarakhovsky, Alexander; Prinjha, Rab K.

The existence of histone-like SLiMs (histone mimics) in nonhistone proteins was first demonstrated in our studies that revealed the presence of a histone H3-like sequence within the histone methyltransferase G9a, which catalyzes dimethylation at lysine 9 of histone H3 (Sampath et al., 2007; Fig. 2 A) . G9a carries a 163-ARKT-166 motif that resembles the 7-ARKS-10 motif of its histone H3 target. Consistent with the presence of the histone mimic, G9a can automethylate itself on lysine 165 (Sampath et al., 2007) , and this methylation facilitates the formation of a repressor complex between G9a and chromodomain-containing protein HP1γ (Sampath et al., 2007; Fig. 2 A) . The H3-like sequence in G9a is also conserved in its homologue and heterodimerization partner GLP (Sampath et al., 2007) , although the two proteins share relatively poor primary sequence conservation in their N-terminal domains. The initial discovery of histone mimics in G9a/GLP led to the identification of numerous histone mimics in other nuclear and nonnuclear proteins, where they contribute to protein-protein interactions or protein stability (Dzimiri and Odenthal, 1990; Lee et al., 2010; Shi et al., 2014) .