title: The JmjC domain protein Epe1 prevents unregulated assembly and disassembly of heterochromatin.
abstract: Heterochromatin normally has prescribed chromosomal positions and must not encroach on adjacent regions. We demonstrate that the fission yeast protein Epe1 stabilises silent chromatin, preventing the oscillation of heterochromatin domains. Epe1 loss leads to two contrasting phenotypes: alleviation of silencing within heterochromatin and expansion of silent chromatin into neighbouring euchromatin. Thus, we propose that Epe1 regulates heterochromatin assembly and disassembly, thereby affecting heterochromatin integrity, centromere function and chromosome segregation fidelity. Epe1 regulates the extent of heterochromatin domains at the level of chromatin, not via the RNAi pathway. Analysis of an ectopically silenced site suggests that heterochromatin oscillation occurs in the absence of heterochromatin boundaries. Epe1 requires predicted iron- and 2-oxyglutarate (2-OG)-binding residues for in vivo function, indicating that it is probably a 2-OG/Fe(II)-dependent dioxygenase. We suggest that, rather than being a histone demethylase, Epe1 may be a protein hydroxylase that affects the stability of a heterochromatin protein, or protein-protein interaction, to regulate the extent of heterochromatin domains. Thus, Epe1 ensures that heterochromatin is restricted to the domains to which it is targeted by RNAi.
authors.affiliation: Wellcome Trust Centre for Cell Biology, The University of Edinburgh, Edinburgh, UK. strewick@staffmail.ed.ac.uk
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Trewick
authors.forename: Elsa
authors.initials: E
authors.lastname: Minc
authors.forename: Richard
authors.initials: R
authors.lastname: Antonelli
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
authors.forename: Robin C
authors.initials: RC
authors.lastname: Allshire
mesh_terms: D002503:Centromere; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006570:Heterochromatin; D007656:Ketoglutaric Acids; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C475031:epe1 protein, S pombe; C400810:ura4 protein, S pombe; D007501:Iron