Harnessing natural variation to identify cis regulators of sex-biased gene expression in a multi-strain mouse liver model
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ABSTRACT:
PROVIDER: PRJNA542063 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9030040_1.fastq.gz | Fastqsanger.gz | |||
| SRR9030040_2.fastq.gz | Fastqsanger.gz | |||
| SRR9030050_1.fastq.gz | Fastqsanger.gz | |||
| SRR9030050_2.fastq.gz | Fastqsanger.gz | |||
| SRR9030100_1.fastq.gz | Fastqsanger.gz |
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Project description:Sex differences in gene expression are widespread in the liver, where many autosomal factors act in tandem with growth hormone signaling to regulate individual variability of sex differences in liver metabolism and disease. Here, we compare hepatic transcriptomic and epigenetic profiles of mouse strains C57BL/6J and CAST/EiJ, representing two subspecies separated by 0.5-1 million years of evolution, to elucidate the actions of genetic factors regulating liver sex differences. We identify 144 protein coding genes and 78 lncRNAs showing strain-conserved sex bias; many have gene ontologies relevant to liver function, are more highly liver-specific and show greater sex bias, and are more proximally regulated than genes whose sex bias is strain-dependent. The strain-conserved genes include key growth hormone-dependent transcriptional regulators of liver sex bias; however, three other transcription factors, Trim24, Tox, and Zfp809, lose their sex-biased expression in CAST/EiJ mouse liver. To elucidate the observed strain specificities in expression, we characterized the strain-dependence of sex-biased chromatin opening and enhancer marks at cis regulatory elements (CREs) within expression quantitative trait loci (eQTL) regulating liver sex-biased genes. Strikingly, 208 of 286 eQTLs with strain-specific, sex-differential effects on expression were associated with a complete gain, loss, or reversal of the sex differences in expression between strains. Moreover, 166 of the 286 eQTLs were linked to the strain-dependent gain or loss of localized sex-biased CREs. Remarkably, a subset of these CREs apparently lacked strain-specific genetic variants yet showed coordinated, strain-dependent sex-biased epigenetic regulation. Thus, we directly link hundreds of strain-specific genetic variants to the high variability in CRE activity and expression of sex-biased genes and uncover underlying genetically-determined epigenetic states controlling liver sex bias in genetically diverse mouse populations.
| S-EPMC8664386 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-10-27 | GSE130914 | GEO
Project description:Investigatation into how genes with sex-differential expression profiles are distributed among the chromosomes in Drosophila. Assayed the expression of 14,142 predicted transcripts in competitive hybridizations and found a dramatic underrepresentation of X-chromosome genes showing high relative expression in male. This is the first report of sex-biased expression of the full (predicted) genome. Findings indicate that there is significant sex-biased expression, especially in gonads. Genes showing sex-biased gene expression profiles are likely to have sex-biased functions. Keywords: other
2003-06-02 | GSE442 | GEO
Project description:Background: Stalk-eyed flies (family Diopsidae) are a model system for studying sexual selection due to the presence of elongated and sexually dimorphic eye-stalks in many species. Recent genomic studies on these flies have revealed a neo-X chromosome and evidence of gene movement onto or off of this X chromosome. To determine if sex linkage and gene movement are related to sexual dimorphism and sexual conflict, we compared gene expression between males and females using oligonucleotide microarrays and RNA from either developing eyestalk tissue or adult heads from a dimorphic species, Teleopsis dalmanni, or from developing eyestalk tissue in a congeneric monomorphic species, T. quinqueguttata. Results: Comparison of gene expression between the sexes for 3,748 genes indicates that dosage compensation is present due to elevated expression of X-linked genes in males. However, sex-biased expression was detected in 26% of the genes present in eye-antennal imaginal discs of larval T. dalmanni. Functional annotation reveals that female-biased genes are associated with transcription, anatomical development and cell communication in the nucleus, while male-biased genes are associated with metabolism and the mitochondria. Comparison of gene expression between experiments identified 140 genes with concordant sex-biased expression in the larval and adult tissues of T. dalmanni and 17 genes with identical sex-biased expression between species. There were only five reversals of sex-biased expression across experiments. In T. dalmanni, male-biased genes are more common on autosomes than on the X while female-biased genes are more common on the X in T. quinqueguttata. Female-biased expression is especially common among genes that moved onto the ancestral X while male-biased expression is more common among genes that moved onto an autosome. Conclusions: Genes with sex-biased expression exhibit different functions in each sex as expected if sexual conflict has influenced their evolution. The strong relationship between sex-biased expression and gene movement found in this study is consistent with resolution of sexual conflict by an RNA- or DNA-mediated process that moves genes between chromosomes. Measurement of gene expression in additional species should provide a more complete picture of how gene expression change occurs over evolutionary time in these extraordinary flies. Two-condition experiment, female vs. male RNA using larval eye discs for two species (Teleopsis dalmanni, Teleopsis quinqueguttata), and adult heads for one species (Teleopsis dalmanni).
2012-04-09 | E-GEOD-37121 | biostudies-arrayexpress
Project description:Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing dataset to analyse male and female miRNA expression profiles in mouse, opossum and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, especially in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that autosomal testis-biased miRNAs tend to be somatically male-biased, whereas autosomal ovary-biased miRNAs are female-biased, possibly due to broad hormonal control. In chicken, which has a Z/W sex chromosome system, expression output of genes on the Z chromosome is expected to be male-biased, since there is no global dosage compensation mechanism that restores expression in ZW females after almost all genes on the W chromosome decayed. Nevertheless, we found that the dominant liver miRNA, miR-122-5p, is Z-linked but expressed in an unbiased manner, due to the unusual retention of a W-linked copy. Another Z-linked miRNA, the male-biased miR-2954-3p, shows conserved preference for dosage-sensitive genes on the Z chromosome, based on computational and experimental data from chicken and zebra finch, and acts to equalise male-to-female expression ratios of its targets. Unexpectedly, our findings thus establish miRNA regulation as a novel gene-specific dosage compensation mechanism.
2017-11-01 | GSE102062 | GEO
Project description:Genes with sex-biased expression in adults experience unique evolutionary dynamics. It is unclear, however, whether the selection pressures responsible for these well documented patterns also act upon genes with sex-biased expression in other developmental stages. To examine this, we measured expression in male and female Drosophila melanogaster larvae.
2012-04-08 | GSE31722 | GEO
Project description:Extensive sex-biased expression has been seen in multiple surveys D. melanogaster. We were interested in broadly sampling sex-biased expression of orthologs and species- or lineage-specific genes in the Drosophila genus. To appropriately assay gene expression in multiple species, we used custom microarrays designed against each of six species that broadly sample the phylogenetic space represented by the newly completed genomes (D. simulans, D. yakuba, D. ananassae, D. pseudoobscura, D. virilis and D. mojavensis) and an array designed against D. melanogaster to determine the overall patterns of sex-biased expression in those species and their chromosome linkage. Keywords: other
2007-11-08 | GSE6640 | GEO
Project description:Investigation of sex-biased expression across species have relied on measurements from whole flies which sample the extensive expression differences found in the germline and gonads of females and males. We wanted to examine genes with sex-biased expression in a somatic tissue to analyze patterns of genes with sex-biased expression in the context of a tissue more phenotypically similar between females and males. We used a Nimblegen microarray designed for Drosophila melanogaster and two custom micoarrays designed for D. pseudoobscura and D. mojavensis to survey gene expression differences in heads of females and males. PolyA+ mRNA was isolated in quadruplicate from dissected heads of 8 day old adult females and males. Female and male mRNA were labeled with Cy3 or Cy5 dyes separately and co-hybridized to species-specific microarrays. We analyzed a total of 24 channels of data.
2010-07-30 | E-GEOD-23309 | biostudies-arrayexpress
Project description:Extensive sex-biased expression has been seen in multiple surveys D. melanogaster. We were interested in broadly sampling sex-biased expression of orthologs and species- or lineage-specific genes in the Drosophila genus. To appropriately assay gene expression in multiple species, we used custom microarrays designed against each of six species that broadly sample the phylogenetic space represented by the newly completed genomes (D. simulans, D. yakuba, D. ananassae, D. pseudoobscura, D. virilis and D. mojavensis) and an array designed against D. melanogaster to determine the overall patterns of sex-biased expression in those species and their chromosome linkage. Keywords: other PolyA+ mRNA in duplicate were isolated from 5-7 day old adult females and males of seven drosophila species. Male and female mRNA was labeled by Cy3 or Cy5 dye separately and hybridized simultaneously to the appropriate species-specific arrays. We performed at least four two-channel hybridizations for each species including two biological replicates and dye-swaps for each of them. Only single channels which passed stringent pre-processing quality control were used. A total of 67 channels of data were used in the final analysis.
2007-11-07 | E-GEOD-6640 | biostudies-arrayexpress
Project description:Although not all sex-dependent gene expression is adaptive, it is likely an important genomic mechanism that allows each sex to independently adapt to environmental changes. Among Drosophila species, sex-biased genes display remarkably consistent evolutionary patterns; male-biased genes evolve faster than unbiased genes in both coding sequence and expression level, suggesting sex-differences in selection through time. However, comparatively little is known of the evolutionary process shaping sex-biased expression within species. Latitudinal clines offer an opportunity to examine how changes in key ecological parameters also influence sex-specific selection and the evolution of sex-biased gene expression. We assayed male and female gene expression in Drosophila serrata along a latitudinal gradient in eastern Australia spanning most of its endemic distribution. Analysis of 11,631 genes across eight populations revealed strong sex differences in the frequency, mode, and strength of divergence. Divergence was far stronger in males than females and while latitudinal clines were evident in both sexes, male divergence was often population-specific, suggesting responses to localized selection pressures that do not covary predictably with latitude. While divergence was enriched for male-biased genes, there was no overrepresentation of X-linked genes in males. By contrast, X-linked divergence was elevated in females, especially for female biased genes. Many genes that diverged in D. serrata have homologs also showing latitudinal divergence in D. simulans and D. melanogaster on other continents, likely indicating parallel adaptation in these distantly related species. Our results suggest that sex differences in selection play an important role in shaping the evolution of gene expression over macro- and micro-ecological spatial scales.
2017-01-04 | GSE90733 | GEO