title: MSL complex is attracted to genes marked by H3K36 trimethylation using a sequence-independent mechanism.
abstract: In Drosophila, X chromosome dosage compensation requires the male-specific lethal (MSL) complex, which associates with actively transcribed genes on the single male X chromosome to upregulate transcription approximately 2-fold. We found that on the male X chromosome, or when MSL complex is ectopically localized to an autosome, histone H3K36 trimethylation (H3K36me3) is a strong predictor of MSL binding. We isolated mutants lacking Set2, the H3K36me3 methyltransferase, and found that Set2 is an essential gene in both sexes of Drosophila. In set2 mutant males, MSL complex maintains X specificity but exhibits reduced binding to target genes. Furthermore, recombinant MSL3 protein preferentially binds nucleosomes marked by H3K36me3 in vitro. Our results support a model in which MSL complex uses high-affinity sites to initially recognize the X chromosome and then associates with many of its targets through sequence-independent features of transcribed genes.
authors.affiliation: Howard Hughes Medical Institute, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Larschan
authors.forename: Artyom A
authors.initials: AA
authors.lastname: Alekseyenko
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Gortchakov
authors.forename: Shouyong
authors.initials: S
authors.lastname: Peng
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Pok
authors.initials: P
authors.lastname: Yang
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: D000818:Animals; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes; D014960:X Chromosome
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; C092595:Pabp2 protein, Drosophila; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C082132:msl-1 protein, Drosophila; C094166:msl-2 protein, Drosophila; C093904:msl-3 protein, Drosophila; D011495:Histone-Lysine N-Methyltransferase; C521696:Set2 protein, Drosophila