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Abstract
Recent studies have indicated that nucleosome turnover is rapid, occurring several
times per cell cycle. To access the effect of nucleosome turnover on the epigenetic
landscape, we investigated H3K79 methylation, which is produced by a single methyltransferase
(Dot1l) with no known demethylase. Using chemical-induced proximity (CIP), we find
that the valency of H3K79 methylation (mono-, di-, and tri-) is determined by nucleosome
turnover rates. Furthermore, propagation of this mark is predicted by nucleosome turnover
simulations over the genome and accounts for the asymmetric distribution of H3K79me
toward the transcriptional unit. More broadly, a meta-analysis of other conserved
histone modifications demonstrates that nucleosome turnover models predict both valency
and chromosomal propagation of methylation marks. Based on data from worms, flies,
and mice, we propose that the turnover of modified nucleosomes is a general means
of propagation of epigenetic marks and a determinant of methylation valence.