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Faucillion, Marie-Line
Publications (3 of 3) Show all publications
Kim, M., Faucillion, M.-L. & Larsson, J. (2018). RNA-on-X 1 and 2 in Drosophila melanogaster fulfill separate functions in dosage compensation. PLoS Genetics, 14(12), Article ID e1007842.
Open this publication in new window or tab >>RNA-on-X 1 and 2 in Drosophila melanogaster fulfill separate functions in dosage compensation
2018 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 14, no 12, article id e1007842Article in journal (Refereed) Published
Abstract [en]

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 Dmelanogaster. 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 roX2mutant, 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.

Place, publisher, year, edition, pages
Public Library Science, 2018
National Category
Genetics
Identifiers
urn:nbn:se:umu:diva-155778 (URN)10.1371/journal.pgen.1007842 (DOI)000455099000025 ()30532158 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2014.0018Swedish Research Council, 2016-03306Swedish Cancer Society, CAN 2017/342
Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved
Faucillion, M.-L. & Larsson, J. (2015). Increased expression of X-linked genes in mammals is associated with a higher stability of transcripts and an increased ribosome density. Genome Biology and Evolution, 7(4), 1039-1052
Open this publication in new window or tab >>Increased expression of X-linked genes in mammals is associated with a higher stability of transcripts and an increased ribosome density
2015 (English)In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 7, no 4, p. 1039-1052Article in journal (Refereed) Published
Abstract [en]

Mammalian sex chromosomes evolved from the degeneration of one homolog of a pair of ancestral autosomes, the proto-Y. This resulted in a gene dose imbalance that is believed to be restored (partially or fully) through up-regulation of gene expression from the single active X-chromosome in both sexes by a dosage compensatory mechanism. We analyzed multiple genome-wide RNA stability datasets and found significantly longer average half-lives for X-chromosome transcripts than for autosomal transcripts in various human cell lines, both male and female, and in mice. Analysis of ribosome profiling data shows that ribosome density is higher on X-chromosome transcripts than on autosomal transcripts in both humans and mice, suggesting that the higher stability is causally linked to a higher translation rate. Our results and observations are in accordance with a dosage compensatory upregulation of expressed X-linked genes. We therefore propose that differential mRNA stability and translation rates of the autosomes and sex chromosomes contribute to an evolutionarily conserved dosage compensation mechanism in mammals.

Place, publisher, year, edition, pages
Oxford University Press, 2015
Keywords
dosage compensation, RNA stability, sex chromosomes, RNA half-life, ribosome density
National Category
Genetics Evolutionary Biology
Research subject
Genetics
Identifiers
urn:nbn:se:umu:diva-101245 (URN)10.1093/gbe/evv054 (DOI)000355148800010 ()25786432 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2015-03-26 Created: 2015-03-26 Last updated: 2018-06-07Bibliographically approved
Lundberg, L. E., Kim, M., Johansson, A.-M., Faucillion, M.-L., Josupeit, R. & Larsson, J. (2013). Targeting of painting of fourth to roX1 and roX2 proximal sites suggests evolutionary links between dosage compensation and the regulation of the 4th chromosome in Drosophila melanogaster. G3: Genes, Genomes, Genetics, 3(8), 1325-1334
Open this publication in new window or tab >>Targeting of painting of fourth to roX1 and roX2 proximal sites suggests evolutionary links between dosage compensation and the regulation of the 4th chromosome in Drosophila melanogaster
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2013 (English)In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 3, no 8, p. 1325-1334Article in journal (Refereed) Published
Abstract [en]

In Drosophila melanogaster, two chromosome-specific targeting and regulatory systems have been described. The male-specific lethal (MSL) complex supports dosage compensation by stimulating gene expression from the male X-chromosome and the protein Painting of fourth (POF) specifically targets and stimulates expression from the heterochromatic 4(th) chromosome. The targeting sites of both systems are well characterized, but the principles underlying the targeting mechanisms have remained elusive. Here we present an original observation, namely that POF specifically targets two loci on the X-chromosome, PoX1 and PoX2 (POF-on-X). PoX1 and PoX2 are located close to the roX1 and roX2 genes, which encode ncRNAs important for the correct targeting and spreading of the MSL-complex. We also found that the targeting of POF to PoX1 and PoX2 is largely dependent on roX expression and identified a high-affinity target region which ectopically recruits POF. The results presented support a model linking the MSL-complex to POF and dosage compensation to regulation of heterochromatin.

Keywords
Painting of fourth, dosage compensation, heterochromatin, epigenetics, Drosophila melanogaster
National Category
Genetics
Research subject
Genetics
Identifiers
urn:nbn:se:umu:diva-72725 (URN)10.1534/g3.113.006866 (DOI)000322822300015 ()23733888 (PubMedID)
Available from: 2013-06-10 Created: 2013-06-10 Last updated: 2018-06-08Bibliographically approved
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