MSL Complex Associates with Clusters of Actively Transcribed Genes along the Drosophila Male X Chromosome

Abstract

Dosage compensation in Drosophila serves as a model system for understanding the targeting of chromatin-modifying complexesto their sites of action. The MSL (male-specific lethal) complex up-regulates transcription of the single male X chromosome,thereby equalizing levels of transcription of X-linked genes between the sexes. Recruitment of the MSL complex toits binding sites on the male X chromosome requires each of the MSL proteins and at least one of the two large noncodingroX RNAs. To better understand how the MSL complex specifically targets the X chromosome, we have defined the bindingusing high-resolution genomic tiling arrays. Our results indicate that the MSL complex largely associates with transcribedgenes that are present in clusters along the X chromosome. We hypothesize that after initial recruitment of the MSL complexto the X chromosome by unknown mechanisms, nascent transcripts or chromatin marks associated with active transcriptionattract the MSL complex to its final targets. Defining MSL-complex-binding sites will provide a tool for understanding functionsof large noncoding RNAs that have remained elusive.