title: Heterochromatin formation in Drosophila is initiated through active removal of H3K4 methylation by the LSD1 homolog SU(VAR)3-3.
abstract: Epigenetic indexing of chromatin domains by histone lysine methylation requires the balanced coordination of methyltransferase and demethylase activities. Here, we show that SU(VAR)3-3, the Drosophila homolog of the human LSD1 amine oxidase, demethylates H3K4me2 and H3K4me1 and facilitates subsequent H3K9 methylation by SU(VAR)3-9. Su(var)3-3 mutations suppress heterochromatic gene silencing, display elevated levels of H3K4me2, and prevent extension of H3K9me2 at pericentric heterochromatin. SU(VAR)3-3 colocalizes with H3K4me2 in interband regions and is abundant during embryogenesis and in syncytial blastoderm, where it appears concentrated at prospective heterochromatin during cycle 14. In embryos of Su(var)3-3/+ females, H3K4me2 accumulates in primordial germ cells, and the deregulated expansion of H3K4me2 antagonizes heterochromatic H3K9me2 in blastoderm cells. Our data indicate an early developmental function for the SU(VAR)3-3 demethylase in controlling euchromatic and heterochromatic domains and reveal a hierarchy in which SU(VAR)3-3-mediated removal of activating histone marks is a prerequisite for subsequent heterochromatin formation by H3K9 methylation.
authors: Institute of Biology, Developmental Genetics, Martin Luther University Halle, D-06120 Halle, Germany.
authors: Thomas
authors: T
authors: Rudolph
authors: Masato
authors: M
authors: Yonezawa
authors: Sandro
authors: S
authors: Lein
authors: Kathleen
authors: K
authors: Heidrich
authors: Stefan
authors: S
authors: Kubicek
authors: Christiane
authors: C
authors: Schäfer
authors: Sameer
authors: S
authors: Phalke
authors: Matthias
authors: M
authors: Walther
authors: Andreas
authors: A
authors: Schmidt
authors: Thomas
authors: T
authors: Jenuwein
authors: Gunter
authors: G
authors: Reuter
mesh_terms: D000818:Animals; D019175:DNA Methylation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D022041:Euchromatin / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism*; D056466:Histone Demethylases; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics*; D008954:Models, Biological; D015394:Molecular Structure; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D022041:Euchromatin; D006570:Heterochromatin; D006657:Histones; D056466:Histone Demethylases; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating; D008780:Methyltransferases