PT  - JOURNAL ARTICLE
AU  - Emma J. Chory
AU  - Joseph P. Calarco
AU  - Nathaniel A. Hathaway
AU  - Oliver Bell
AU  - Dana S. Neel
AU  - Gerald R. Crabtree
TI  - Nucleosome turnover is sufficient to establish varied histone methylation states
AID  - 10.1101/256321
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 256321
4099  - http://biorxiv.org/content/early/2018/01/31/256321.short
4100  - http://biorxiv.org/content/early/2018/01/31/256321.full
AB  - Transcription-dependent methylation of histone H3 at lysine 79 (H3K79) is evolutionarily conserved from yeast to mammals, critical for normal development and frequently deregulated by genetic recombination in Mixed Lineage Leukemia. Although this histone modification is associated with gene activity, little is known about the cellular mechanisms of H3K79 methylation regulation. Because no H3K79 demethylase has been discovered, the mechanism of its removal remains unclear. Utilizing chemical-induced-proximity to control histone methylation in vivo we show that the dynamics of methylation state (mono, di, tri-methylation) is genome-context specific. Further, Monte Carlo simulations coupling systems of kinetic reactions with histone turnover rates, suggest that nucleo-some turnover is sufficient to establish varied genome-wide methylation states without active demethylation.