AbstractHyperactivity of the single X-chromosome in maleDrosophilais achieved by establishing a ribonucleoprotein complex, called Dosage Compensation Complex (DCC), on the male X chromosome. Msl-1 and Msl-2 proteins, involved in the initiation and establishing of DCC on male X chromosome, are very crucial component of this complex. In the present study, it has been found here that a long non-coding RNA genehsrωgenetically interacts with Msl-1 as well as Msl-2 and suppresses the lethal phenotype of Msl-1 or Msl-2 down-regulation in its up-regulated background. Additionally, it is also found here that an ATP-dependent chromatin remodeler, NURF301, also interacts withhsrωin same manner. General lethality caused byAct-GAL4driven global expression ofNURF301-RNAiand the male-specific lethality followingMsl-1-RNAiorMsl-2-RNAitransgene expression were partially suppressed by over-expression ofhsrω, but not by down regulation throughhsrω-RNAi. Likewise, eye phenotypes followingey-GAL4driven down-regulation ofNURF301orMsl-1orMsl-2were also partially suppressed by over-expression ofhsrω.Act-GAL4driven global over-expression ofhsrωalong withMsl-1-RNAiorMsl-2-RNAitransgene substantially restored levels of MSL-2 protein on the male X chromosome. Similarly, levels and distribution of Megator protein, which was reduced and distribution at nuclear rim and in nucleoplasm was affected in the MT and SG nuclei, is also restored when hsrω transcripts are down-regulated inAct-GAL4drivenMsl-1-RNAiorMsl-2-RNAigenetic background. NURF301, a known chromatin remodeler, when down-regulated shows decondensed X chromosome in male larvae. Down-regulation of hsrω results in restoration of chromosome architecture without affecting the level of ISWI protein-another chromatin remodeler protein, known to interacting with hsrω.