title: Su(var) genes regulate the balance between euchromatin and heterochromatin in Drosophila.
abstract: Histone lysine methylation is an epigenetic mark to index chromosomal subdomains. In Drosophila, H3-K9 di- and trimethylation is mainly controlled by the heterochromatic SU(VAR)3-9 HMTase, a major regulator of position-effect variegation (PEV). In contrast, H3-K27 methylation states are independently mediated by the Pc-group enzyme E(Z). Isolation of 19 point mutants demonstrates that the silencing potential of Su(var)3-9 increases with its associated HMTase activity. A hyperactive Su(var)3-9 mutant, pitkin(D), displays extensive H3-K9 di- and trimethylation within but also outside pericentric heterochromatin. Notably, mutations in a novel Su(var) gene, Su(var)3-1, severely restrict Su(var)3-9-mediated gene silencing. Su(var)3-1 was identified as "antimorphic" mutants of the euchromatic H3-S10 kinase JIL-1. JIL-1(Su(var)3-1) mutants maintain kinase activity and do not detectably impair repressive histone lysine methylation marks. However, analyses with seven different PEV rearrangements demonstrate a general role of JIL-1(Su(var)3-1) in controlling heterochromatin compaction and expansion. Our data provide evidence for a dynamic balance between heterochromatin and euchromatin, and define two distinct mechanisms for Su(var) gene function. Whereas the majority of Su(var)s encode inherent components of heterochromatin that can establish repressive chromatin structures [intrinsic Su(var)s], Su(var)3-1 reflects gain-of-function mutants of a euchromatic component that antagonize the expansion of heterochromatic subdomains [acquired Su(var)s].
authors.affiliation: Institute of Genetics, Biologicum, Martin Luther University Halle, D-06120 Halle, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Ebert
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schotta
authors.forename: Sandro
authors.initials: S
authors.lastname: Lein
authors.forename: Stefan
authors.initials: S
authors.lastname: Kubicek
authors.forename: Veiko
authors.initials: V
authors.lastname: Krauss
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
authors.forename: Gunter
authors.initials: G
authors.lastname: Reuter
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D022041:Euchromatin / Q000378:metabolism*; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D022041:Euchromatin; D006570:Heterochromatin; D008780:Methyltransferases