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Nucleosome turnover is sufficient to establish varied histone methylation states

View ORCID ProfileEmma J. Chory, Joseph P. Calarco, View ORCID ProfileNathaniel A. Hathaway, View ORCID ProfileOliver Bell, Dana S. Neel, View ORCID ProfileGerald R. Crabtree
doi: https://doi.org/10.1101/256321
Emma J. Chory
1Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
2Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA
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Joseph P. Calarco
2Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA
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Nathaniel A. Hathaway
3Division of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina 27599, United States
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Oliver Bell
4Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), A-1030 Vienna, Austria
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Dana S. Neel
2Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA
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Gerald R. Crabtree
2Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA
5Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
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  • For correspondence: crabtree@stanford.edu
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Abstract

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.

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Posted January 31, 2018.
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Nucleosome turnover is sufficient to establish varied histone methylation states
Emma J. Chory, Joseph P. Calarco, Nathaniel A. Hathaway, Oliver Bell, Dana S. Neel, Gerald R. Crabtree
bioRxiv 256321; doi: https://doi.org/10.1101/256321
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Nucleosome turnover is sufficient to establish varied histone methylation states
Emma J. Chory, Joseph P. Calarco, Nathaniel A. Hathaway, Oliver Bell, Dana S. Neel, Gerald R. Crabtree
bioRxiv 256321; doi: https://doi.org/10.1101/256321

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