Abstract
In Drosophila melanogaster, the male-specific lethal (MSL) complex plays a key role in dosage compensation by stimulating expression of male X-chromosome genes. It consists of MSL proteins and two long noncoding RNAs, roX1 and roX2, that are required for spreading of the complex on the chromosome and are redundant in the sense that loss of either does not affect male viability. However, despite rapid evolution, both roX species are present in diverse Drosophilidae species, raising doubts about their full functional redundancy. Thus, we have investigated consequences of deleting roX1 and/or roX2 to probe their specific roles and redundancies in D. melanogaster. We have created a new mutant allele of roX2 and show that roX1 and roX2 have partly separable functions in dosage compensation. In larvae, roX1 is the most abundant variant and the only variant present in the MSL complex when the complex is transmitted (physically associated with the X-chromosome) in mitosis. Loss of roX1 results in reduced expression of the genes on the X-chromosome, while loss of roX2 leads to MSL-independent upregulation of genes with male-biased testis-specific transcription. In roX1 roX2 mutant, gene expression is strongly reduced in a manner that is not related to proximity to high-affinity sites. Our results suggest that high tolerance of mis-expression of the X-chromosome has evolved. We propose that this may be a common property of sex-chromosomes, that dosage compensation is a stochastic process and its precision for each individual gene is regulated by the density of high-affinity sites in the locus.
Highlights
In eukaryotic genomes several long non-coding RNAs are associated with chromatin and involved in gene expression regulation, but the mechanisms involved are largely unknown
In roX1 roX2 mutant, gene expression is strongly reduced in a manner that is not related to proximity to high-affinity sites
As cytological band 10C is the location of the roX2 gene, this implies that roX2 is favored in male-specific lethal (MSL) complexes targeting the roX2 region rather than roX1
Summary
In eukaryotic genomes several long non-coding RNAs (lncRNAs) are associated with chromatin and involved in gene expression regulation, but the mechanisms involved are largely unknown. In both mammals and fruit flies, they are required to identify and mark X-chromosomes for dosage compensation, a mechanism that helps maintain balanced expression of the genome. Some genes located on the X-chromosome are expressed in a sex-specific mode, equal expression of most of the genes in males and females is required [1, 2]. One of the pair of X-chromosomes in females is largely silenced through random X-chromosome inactivation, a mechanism that involves at least three lncRNAs [5, 6]. The long noncoding Xist RNA, plays a key role in marking one of the X-chromosomes and recruiting Polycomb repressive complex 2, thereby mediating its inactivation by histone H3 lysine 27 methylation [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
