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Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden..
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2010 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 11, no 1, 614- p.Article in journal (Refereed) Published
Abstract [en]

Background:

Sexual dimorphism in brain gene expression has been recognized in several animal species.However, the relevant regulatory mechanisms remain poorly understood. To investigatewhether sex-biased gene expression in mammalian brain is globally regulated or locallyregulated in diverse brain structures, and to study the genomic organisation of brain-expressedsex-biased genes, we performed a large scale gene expression analysis of distinct brainregions in adult male and female mice.

Results:

This study revealed spatial specificity in sex-biased transcription in the mouse brain, andidentified 173 sex-biased genes in the striatum; 19 in the neocortex; 12 in the hippocampusand 31 in the eye. Genes located on sex chromosomes were consistently over-represented inall brain regions. Analysis on a subset of genes with sex-bias in more than one tissue revealedY-encoded male-biased transcripts and X-encoded female-biased transcripts known to escapeX-inactivation. In addition, we identified novel coding and non-coding X-linked genes withfemale-biased expression in multiple tissues. Interestingly, the chromosomal positions of allof the female-biased non-coding genes are in close proximity to protein-coding genes thatescape X-inactivation. This defines X-chromosome domains each of which contains a codingand a non-coding female-biased gene. Lack of repressive chromatin marks in non-codingtranscribed loci supports the possibility that they escape X-inactivation. Moreover, RNADNAcombined FISH experiments confirmed the biallelic expression of one such noveldomain.

Conclusion:

This study demonstrated that the amount of genes with sex-biased expression variesbetween individual brain regions in mouse. The sex-biased genes identified are localized onmany chromosomes. At the same time, sexually dimorphic gene expression that is common toseveral parts of the brain is mostly restricted to the sex chromosomes. Moreover, the studyuncovered multiple female-biased non-coding genes that are non-randomly co-localized onthe X-chromosome with protein-coding genes that escape X-inactivation. This raises thepossibility that expression of long non-coding RNAs may play a role in modulating geneexpression in domains that escape X-inactivation in mouse.

Place, publisher, year, edition, pages
2010. Vol. 11, no 1, 614- p.
Keyword [en]
long non-coding RNA, X-inactivation, female-biased, sex-biased, gene, gene expression, lncRNA, noncoding RNA, X-chromosome, brain, sex, hippocampus, neocortex, striatum, eye, lung, escape X-inactivation, domains
National Category
Medical and Health Sciences Biological Sciences
Research subject
Genetics; Biology with specialization in Animal Development; Neuroscience
Identifiers
URN: urn:nbn:se:uu:diva-133284DOI: 10.1186/1471-2164-11-614ISI: 000284579400001PubMedID: 21047393OAI: oai:DiVA.org:uu-133284DiVA: diva2:360920
Available from: 2010-11-05 Created: 2010-11-05 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Sexually Dimorphic Gene Expression in the Mammalian Brain
Open this publication in new window or tab >>Sexually Dimorphic Gene Expression in the Mammalian Brain
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In recent times, major advances have been made towards understanding sexual dimorphism in the brain on a molecular basis. This thesis summarises my modest contributions to these endeavours. Sexual dimorphisms are manifested throughout the spectrum of biological complexity, and can be studied by numerous approaches. The approach of this thesis is to explore sex-biased gene expression in mammalian somatic tissues. Paper I describes an evolutionarily conserved sexual gene expression pattern in the primate brain. Conserved sex-biased genes may underlie important sex differences in neurobiology. In Paper II, Y-chromosome genes expressed across several regions of the human male brain during mid-gestation are identified. Such genes may play male-specific roles during brain development. The studies of Papers III and IV explore sex-biased gene expression in several somatic tissues from mouse. The amount of genes with sex-biased expression varied in different brain regions. The striatum was particularly interesting, with an order of magnitude increase in the number of sex-biased genes as compared to the other included brain regions. Of potentially wider significance are my observations regarding the transcriptional regulation of domains that escape X-chromosome inactivation (XCI). Specifically, I provide the first evidence that long non-coding RNAs (lncRNAs) transcribe together with protein-coding genes in XCI-escaping domains. This raises the possibility that lncRNAs mediate the transcriptional regulation of XCI-escaping domains. I also present evidence that the mouse X-chromosome has undergone both feminisation and de-masculinisation during evolution, as indicated by the sex-skewed regulation of genes on this chromosome. This finding is relevant for understanding the selective forces that shaped the mammalian X-chromosome. In the final chapter, Paper V, the generation of a novel transgenic mouse line, Gpr101-Cre, is described. Its progeny can be used for functional studies of striatum, a brain structure with major sexual dimorphism, as is further demonstrated in the Papers of this thesis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 840
National Category
Developmental Biology
Identifiers
urn:nbn:se:uu:diva-156640 (URN)978-91-554-8118-6 (ISBN)
Public defence
2011-09-16, Zootissalen (EBC 01.01006), Evolutionsbiologiskt centrum, EBC, Norbyvägen, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2011-08-26 Created: 2011-08-04 Last updated: 2011-11-10

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