Non-coding roX RNAs Prevent the Binding of the MSL-complex to Heterochromatic Regions

Long non-coding rnas contribute to dosage compensation in both mammals and drosophila by inducing changes in the chromatin structure of the x-chromosome. in drosophila melanogaster,rox1 and rox2 are long non-coding rnas that together with proteins form the male-specific lethal (msl) complex,which coats the entire male x-chromosome and mediates dosage compensation by increasing its transcriptional output. studies on polytene chromosomes have demonstrated that when both rox1 and rox2 are absent,the msl-complex becomes less abundant on the male x-chromosome and is relocated to the chromocenter and the 4thchromosome. here we address the role of rox rnas in msl-complex targeting and the evolution of dosage compensation in drosophila. we performed chip-seq experiments which showed that msl-complex recruitment to high affinity sites (has) on the x-chromosome is independent of rox and that the has sequence motif is conserved in d. simulans. additionally,a complete and enzymatically active msl-complex is recruited to six specific genes on the 4thchromosome. interestingly,our sequence analysis showed that in the absence of rox rnas,the msl-complex has an affinity for regions enriched in hoppel transposable elements and repeats in general. we hypothesize that rox mutants reveal the ancient targeting of the msl-complex and propose that the role of rox rnas is to prevent the binding of the msl-complex to heterochromatin. © 2014 figueiredo et al.