title: The MSL3 chromodomain directs a key targeting step for dosage compensation of the Drosophila melanogaster X chromosome.
abstract: The male-specific lethal (MSL) complex upregulates the single male X chromosome to achieve dosage compensation in Drosophila melanogaster. We have proposed that MSL recognition of specific entry sites on the X is followed by local targeting of active genes marked by histone H3 trimethylation (H3K36me3). Here we analyze the role of the MSL3 chromodomain in the second targeting step. Using ChIP-chip analysis, we find that MSL3 chromodomain mutants retain binding to chromatin entry sites but show a clear disruption in the full pattern of MSL targeting in vivo, consistent with a loss of spreading. Furthermore, when compared to wild type, chromodomain mutants lack preferential affinity for nucleosomes containing H3K36me3 in vitro. Our results support a model in which activating complexes, similarly to their silencing counterparts, use the nucleosomal binding specificity of their respective chromodomains to spread from initiation sites to flanking chromatin.
authors.affiliation: Harvard-Partners Center for Genetics and Genomics, Division of Genetics, Department of Medicine, Brigham & Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Tuba H
authors.initials: TH
authors.lastname: Sural
authors.forename: Shouyong
authors.initials: S
authors.lastname: Peng
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.forename: Mitzi I
authors.initials: MI
authors.lastname: Kuroda
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006657:Histones / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000378:metabolism; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014960:X Chromosome
chemical_list: D029721:Drosophila Proteins; D006657:Histones; D050505:Mutant Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C093904:msl-3 protein, Drosophila