A Simple Histone Code Opens Many Paths to Epigenetics

• DOI: 10.1371/journal.pcbi.1002643
• Publication Date: 2012-08-16T21:22:06Z
• Authors: Kim Sneppen; Ian B. Dodd
• Keywords: Cooperativity; Histone code; Bistability; Histone Methylation

Nucleosomes can be covalently modified by addition of various chemical groups on several their exposed histone amino acids. These modifications are added and removed enzymes (writers) recognized nucleosome-binding proteins (readers). Linking a reader domain writer that recognize create the same modification state should allow nucleosomes in particular to recruit nearby nucleosomes. This positive feedback has potential provide alternative stable heritable states required for epigenetic memory. However, analysis simple codes involving interconversions between only two or three types revealed few circuit designs bistability. Here we show computer simulations code at positions, producing four states, combined with reader-writer able distinguish these allows hundreds different circuits capable expanded possibilities result from multiple ways generating two-step cooperativity feedback--through pathways an additional, novel motif. Our reveals other properties such circuits. They most robust when dominant nucleosome both positions not type inserted after DNA replication. The often own destroy opposing type, but never catalyze destruction. appear evolutionary accessible; changed stepwise into almost any without losing Thus, our indicates systems utilize have huge identifies critical features systems.