Local spreading of MSL complexes fromroXgenes on theDrosophilaX chromosome

Abstract

MSL proteins and noncoding roX RNAs form complexes to up-regulate hundreds of genes on the Drosophila male X chromosome, and make X-linked gene expression equal in males and females. Altering the ratio of MSL proteins to roX RNA dramatically changes X-chromosome morphology. In protein excess, the MSL complex concentrates near sites of roX transcription and is depleted elsewhere. These results support a model for distribution of MSL complexes, in which local spreading in cis from roX genes is balanced with diffusion of soluble complexes in trans. When overexpressed, MSL proteins can recognize the X chromosome, modify histones, and partially restore male viability even in the absence of roX RNAs. Thus, the protein components can carry out all essential functions of dosage compensation, but roX RNAs facilitate the correct targeting of MSL complexes, in part by nucleation of spreading from their sites of synthesis.Supplemental material is available at http://www.genesdev.org.

Dosage Compensation inDrosophila

“…5E,F) (Park et al 2002). This extensive spreading is augmented by overexpression of MSL1 and MSL2, the key limiting MSL proteins, and diminished by overexpression of roX RNA from competing transgenes, suggesting that successful cotranscriptional assembly of MSL complexes may drive local spreading (Oh et al 2003). The ability of roX genes to direct MSL complexes to the wrong chromosome is one of the most intriguing aspects of the dosage compensation mechanism.…”

“…Partial purification of the complex suggests the presence of a tight core consisting of MSL1, MSL2, MSL3, and MOF proteins, with roX RNA and the MLE helicase lost except under very low salt concentrations (Smith et al 2000). The minimal protein core complex lacking roX RNAs can still specifically acetylate histone H4 on lysine 16 within nucleosomes in vitro (Morales et al 2004), and overexpression of MSL proteins can partially overcome the lack of roX RNAs, suggesting that the proteins possess all of the essential functions of dosage compensation but require the RNAs to stimulate assembly and spreading (Oh et al 2003). Assembly of the complex is initiated when the secondary structure of the roX RNAs is modified, allowing the binding of MSL2 and providing the core for the full recruitment of the other MSL subunits (Ilik et al 2013;Maenner et al 2013).…”

X-chromosome-wide profiling of MSL-1 distribution and dosage compensation inDrosophila

“…However, this model appears now to be too simple. Indeed, any piece of the X chromosome is able to attract the complex when moved onto an autosome, even without any of the 35-40 "entry sites" (Oh et al 2003;Fagegaltier and Baker 2004). Another model to explain MSL targeting has emerged from a recent study, which showed that recruitment of the MSLs can be induced by transcription activation of a transgene inserted in a band normally deprived in MSL (Sass et al 2003).…”

Positive Selection at the Binding Sites of the Male-Specific Lethal Complex Involved in Dosage Compensation in Drosophila

“…The third site is an intergenic region from the 18D10 region of the X chromosome (Oh et al 2004). When a roX or 18D10 transgene is inserted on an autosome, the MSL complex is recruited to this site, and neighboring sites sometimes show MSL binding as well (Kelley et al 1999;Oh et al 2003).…”