title: The MOF chromobarrel domain controls genome-wide H4K16 acetylation and spreading of the MSL complex.
abstract: The histone H4 lysine 16 (H4K16)-specific acetyltransferase MOF is part of two distinct complexes involved in X chromosome dosage compensation and autosomal transcription regulation. Here we show that the MOF chromobarrel domain is essential for H4K16 acetylation throughout the Drosophila genome and is required for spreading of the male-specific lethal (MSL) complex on the X chromosome. The MOF chromobarrel domain directly interacts with nucleic acids and potentiates MOF's enzymatic activity after chromatin binding, making it a unique example of a chromo-like domain directly controlling acetylation activity in vivo. We also show that the Drosophila-specific N terminus of MOF has evolved to perform sex-specific functions. It modulates nucleosome binding and HAT activity and controls MSL complex assembly, thus regulating MOF function in dosage compensation. We propose that MOF has been especially tailored to achieve tight regulation of its enzymatic activity and enable its dual role on X and autosomes.
authors.affiliation: Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Conrad
authors.forename: Florence M G
authors.initials: FM
authors.lastname: Cavalli
authors.forename: Herbert
authors.initials: H
authors.lastname: Holz
authors.forename: Erinc
authors.initials: E
authors.lastname: Hallacli
authors.forename: Jop
authors.initials: J
authors.lastname: Kind
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Ilik
authors.forename: Juan M
authors.initials: JM
authors.lastname: Vaquerizas
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Luscombe
authors.forename: Asifa
authors.initials: A
authors.lastname: Akhtar
mesh_terms: D000107:Acetylation; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D005260:Female; D049750:Genome, Insect; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors; C082132:msl-1 protein, Drosophila; C094166:msl-2 protein, Drosophila; C093904:msl-3 protein, Drosophila; D051548:Histone Acetyltransferases; C111063:mof protein, Drosophila