An H3K9 methylation dependent protein interaction regulates the non-enzymatic function of a putative histone demethylase
- University of Michigan, United States
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 reverses epigenetic silencing. Here, we reveal an inversion of this paradigm where a putative histone demethylase Epe1 in fission yeast, has a non-enzymatic function that opposes heterochromatin assembly. Mutations within the putative catalytic JmjC domain of Epe1 disrupt its interaction with Swi6HP1 suggesting that it might have other functions besides enzymatic activity. The C-terminus of Epe1 directly interacts with Swi6HP1, and H3K9 methylation stimulates this protein-protein interaction in vitro and in vivo. Expressing the Epe1 C-terminus is sufficient to disrupt heterochromatin by outcompeting the histone deacetylase, Clr3 from sites of heterochromatin formation. Our results underscore how histone modifying proteins that resemble enzymes have non-catalytic functions that regulate the assembly of epigenetic complexes in cells.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Kaushik Ragunathan
Funding
The authors declare that there was no external funding for this work.
Copyright
© 2020, Raiymbek et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An H3K9 methylation dependent protein interaction regulates the non-enzymatic function of a putative histone demethylase
eLife 9:e53155.
https://doi.org/10.7554/eLife.53155
