title: Ash2 acts as an ecdysone receptor coactivator by stabilizing the histone methyltransferase Trr.
abstract: The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr and is required for its stabilization. Thus we propose that Ash2 functions together with Trr as an ecdysone receptor coactivator.
authors.affiliation: Departament de Genètica and Institut de Biomedicina, Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Carbonell
authors.forename: Alexander
authors.initials: A
authors.lastname: Mazo
authors.forename: Florenci
authors.initials: F
authors.lastname: Serras
authors.forename: Montserrat
authors.initials: M
authors.lastname: Corominas
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D004440:Ecdysone / Q000502:physiology; D004795:Enzyme Stability; D005260:Female; D005804:Genes, Lethal; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D060227:Imaginal Discs / Q000166:cytology / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D008297:Male; D008745:Methylation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D059007:Polytene Chromosomes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011987:Receptors, Steroid / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014921:Wings, Animal / Q000033:anatomy & histology
chemical_list: D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D011987:Receptors, Steroid; D014157:Transcription Factors; C103604:ash2 protein, Drosophila; C055469:ecdysone receptor; D004440:Ecdysone; D011495:Histone-Lysine N-Methyltransferase; C479519:TRR protein, Drosophila