Non-coding roX RNAs prevent the binding of the MSL-complex to heterochromatic regions
2014 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 12, e1004865- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2014. Vol. 10, no 12, e1004865- p.
Biochemistry and Molecular Biology Genetics Bioinformatics and Systems Biology
IdentifiersURN: urn:nbn:se:umu:diva-93046DOI: 10.1371/journal.pgen.1004865ISI: 000346649900060PubMedID: 25501352ScopusID: 2-s2.0-84919667251OAI: oai:DiVA.org:umu-93046DiVA: diva2:745803
FunderSwedish Research Council, 621-2012-2165
Originally included in thesis in manuscript form.2014-09-112014-09-112015-05-12Bibliographically approved