PT  - JOURNAL ARTICLE
AU  - Gulzhan Raiymbek
AU  - Sojin An
AU  - Nidhi Khurana
AU  - Saarang Gopinath
AU  - Raymond Trievel
AU  - Uhn-soo Cho
AU  - Kaushik Ragunathan
TI  - A non-enzymatic function associated with a putative histone demethylase licenses epigenetic inheritance
AID  - 10.1101/545814
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 545814
4099  - http://biorxiv.org/content/early/2019/02/10/545814.short
4100  - http://biorxiv.org/content/early/2019/02/10/545814.full
AB  - 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.