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A non-enzymatic function associated with a putative histone demethylase licenses epigenetic inheritance

Gulzhan Raiymbek, Sojin An, Nidhi Khurana, Saarang Gopinath, Raymond Trievel, Uhn-soo Cho, Kaushik Ragunathan
doi: https://doi.org/10.1101/545814
Gulzhan Raiymbek
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA
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Sojin An
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA
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Nidhi Khurana
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA
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Saarang Gopinath
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA
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Raymond Trievel
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA
2Department of Biophysics, University of Michigan, Ann Arbor, MI, USA
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Uhn-soo Cho
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA
2Department of Biophysics, University of Michigan, Ann Arbor, MI, USA
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Kaushik Ragunathan
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA
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  • For correspondence: ragunath@umich.edu
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ABSTRACT

H3K9 methylation (H3K9me) specifies the establishment and maintenance of transcriptionally silent epigenetic states or heterochromatin. The enzymatic erasure of histone modifications is widely assumed to be the primary mechanism that resets epigenetic states during and after DNA replication. Here, we demonstrate that a putative histone-demethylase Epe1 in fission yeast, regulates epigenetic inheritance through a non-enzymatic process. Mutations that map to its putative catalytic domain disrupt its interaction with Swi6HP1 and heterochromatin specific pattern of localization without any requirement for enzymatic activity. Epe1 and Swi6HP1 form an inhibitory complex which displaces histone deacetylases from sites of heterochromatin formation. Sequence-specific recruitment of a histone deacetylase, Clr3 renders heterochromatin refractory to the anti-silencing functions of Epe1 and licenses the inheritance of epigenetic states in cis. Epigenetic inheritance solely depends on the read-write activity of the H3K9 methyltransferase Clr4 which competes with genome-wide nucleosome turnover processes in the absence of enzymatic erasure.

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Posted February 10, 2019.
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A non-enzymatic function associated with a putative histone demethylase licenses epigenetic inheritance
Gulzhan Raiymbek, Sojin An, Nidhi Khurana, Saarang Gopinath, Raymond Trievel, Uhn-soo Cho, Kaushik Ragunathan
bioRxiv 545814; doi: https://doi.org/10.1101/545814
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A non-enzymatic function associated with a putative histone demethylase licenses epigenetic inheritance
Gulzhan Raiymbek, Sojin An, Nidhi Khurana, Saarang Gopinath, Raymond Trievel, Uhn-soo Cho, Kaushik Ragunathan
bioRxiv 545814; doi: https://doi.org/10.1101/545814

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