Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

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

MEDICINE

MEDICIN

Biology

Biologi

Genetics

Genetik

Biologi med inriktning mot zoologisk utvecklingsbiologi

Biology with specialization in Animal Development

Neuroscience

Neurovetenskap

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