X-chromosome-wide profiling of MSL-1 distribution and dosage compensation in Drosophila.
In Drosophila, dosage compensation is achieved by a twofold up-regulation of the male X-linked genes and requires the association of the male-specific lethal complex (MSL) on the X chromosome. How the MSL complex is targeted to X-linked genes and whether its recruitment at a local level is necessary and sufficient to ensure dosage compensation remain poorly understood. Here we report the MSL-1-binding profile along the male X chromosome in embryos and male salivary glands isolated from third instar larvae using chromatin immunoprecipitation (ChIP) coupled with DNA microarray (ChIP-chip). This analysis has revealed that majority of the MSL-1 targets are primarily expressed during early embryogenesis and many target genes possess DNA replication element factor (DREF)-binding sites in their promoters. In addition, we show that MSL-1 distribution remains stable across development and that binding of MSL-1 on X-chromosomal genes does not correlate with transcription in male salivary glands. These results show that transcription per se on the X chromosome cannot be the sole signal for MSL-1 recruitment. Furthermore, genome-wide analysis of the dosage-compensated status of X-linked genes in male and female shows that most of the X chromosome remains compensated without direct MSL-1 binding near the gene. Our results, therefore, provide a comprehensive overview of MSL-1 binding and dosage-compensated status of X-linked genes and suggest a more global effect of MSL complex on X-chromosome regulation.
European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Gaëlle
G
Legube
Shannon K
SK
McWeeney
Martin J
MJ
Lercher
Asifa
A
Akhtar
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D017344:Genes, Insect; D007814:Larva / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012469:Salivary Glands / Q000378:metabolism; D012730:Sex Chromosomes / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
C099494:Dref protein, Drosophila; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C082132:msl-1 protein, Drosophila; C093904:msl-3 protein, Drosophila; D004247:DNA