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Conservation of Regional Variation in Sex-Specific Sex Chromosome Regulation.

ABSTRACT: Regional variation in sex-specific gene regulation has been observed across sex chromosomes in a range of animals and is often a function of sex chromosome age. The avian Z chromosome exhibits substantial regional variation in sex-specific regulation, where older regions show elevated levels of male-biased expression. Distinct sex-specific regulation also has been observed across the male hypermethylated (MHM) region, which has been suggested to be a region of nascent dosage compensation. Intriguingly, MHM region regulatory features have not been observed in distantly related avian species despite the hypothesis that it is situated within the oldest region of the avian Z chromosome and is therefore orthologous across most birds. This situation contrasts with the conservation of other aspects of regional variation in gene expression observed on the avian sex chromosomes but could be the result of sampling bias. We sampled taxa across the Galloanserae, an avian clade spanning 90 million years, to test whether regional variation in sex-specific gene regulation across the Z chromosome is conserved. We show that the MHM region is conserved across a large portion of the avian phylogeny, together with other sex-specific regulatory features of the avian Z chromosome. Our results from multiple lines of evidence suggest that the sex-specific expression pattern of the MHM region is not consistent with nascent dosage compensation.

SUBMITTER: Wright AE

PROVIDER: S-EPMC4596671 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Conservation of Regional Variation in Sex-Specific Sex Chromosome Regulation.

Wright Alison E AE Zimmer Fabian F Harrison Peter W PW Mank Judith E JE

Genetics 20150805 2

Regional variation in sex-specific gene regulation has been observed across sex chromosomes in a range of animals and is often a function of sex chromosome age. The avian Z chromosome exhibits substantial regional variation in sex-specific regulation, where older regions show elevated levels of male-biased expression. Distinct sex-specific regulation also has been observed across the male hypermethylated (MHM) region, which has been suggested to be a region of nascent dosage compensation. Intrig ...[more]

PMID: 26245831

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Project description:BackgroundSex differences in pituitary growth hormone (GH) are well documented and coordinate maturation and growth. GH and its receptor are also produced in the brain where they may impact cognitive function and synaptic plasticity, and estradiol produces Gh sex differences in rat hippocampus. In mice, circulating estradiol increases Gh mRNA in female but not in male medial preoptic area (mPOA); therefore, additional factors regulate sexually dimorphic Gh expression in the brain. Thus, we hypothesized that sex chromosomes interact with estradiol to promote sex differences in GH. Here, we assessed the contributions of both estradiol and sex chromosome complement on Gh mRNA levels in three large brain regions: the hippocampus, hypothalamus, and cerebellum.MethodsWe used the four core genotypes (FCG) mice, which uncouple effects of sex chromosomes and gonadal sex. The FCG model has a deletion of the sex-determining region on the Y chromosome (Sry) and transgenic insertion of Sry on an autosome. Adult FCG mice were gonadectomized and given either a blank Silastic implant or an implant containing 17β-estradiol. Significant differences in GH protein and mRNA were attributed to estradiol replacement, gonadal sex, sex chromosome complement, and their interactions, which were assessed by ANOVA and planned comparisons.ResultsEstradiol increased Gh mRNA in the cerebellum and hippocampus, regardless of sex chromosome complement or gonadal sex. In contrast, in the hypothalamus, females had higher Gh mRNA than males, and XY females had more Gh mRNA than XY males and XX females. This same pattern was observed for GH protein. Because the differences in Gh mRNA in the hypothalamus did not replicate prior studies using other mouse models and tissue from mPOA or arcuate nucleus, we examined GH protein in the arcuate, a subdivision of the hypothalamus. Like the previous reports, and in contrast to the entire hypothalamus, a sex chromosome complement effect showed that XX mice had more GH than XY in the arcuate.ConclusionsSex chromosome complement regulates GH in some but not all brain areas, and within the hypothalamus, sex chromosomes have cell-specific actions on GH. Thus, sex chromosome complement and estradiol both contribute to GH sex differences in the brain.

Project description:BackgroundAfrican populations are characterised by diversity at many levels including: demographic history, genetic ancestry, language, wealth, socio-political landscape, culture and behaviour. Several of these have a profound impact on body fat mass. Obesity, a key risk factor for cardiovascular and metabolic diseases, in the wake of the epidemiological and health transitions across the continent, requires detailed analysis together with other major risk factors.ObjectiveTo compare regional and sex-specific body mass index (BMI) distributions, using a cross-sectional study design, in adults aged 40-60 years across six study sites in four sub-Saharan African (SSA) countries and to compare the determinants of BMI at each.MethodsAnthropometric measurements were standardised across sites and BMI calculated. Median BMI and prevalence of underweight, lean, overweight and obesity were compared between the sexes and across sites. Data from multivariable linear regression models for the principal determinants of BMI were summarised from the site-specific studies.ResultsBMI was calculated in 10,702 participants (55% female) and was significantly higher in women than men at nearly all sites. The highest prevalence of obesity was observed at the three South African sites (42.3-66.6% in women and 2.81-17.5% in men) and the lowest in West Africa (1.25-4.22% in women and 1.19-2.20% in men). Across sites, higher socio-economic status and educational level were associated with higher BMI. Being married and increased dietary intake were associated with higher BMI in some communities, whilst smoking and alcohol intake were associated with lower BMI, as was HIV infection in the regions where it was prevalent.ConclusionIn SSA there is a marked variation in the prevalence of obesity both regionally and between men and women. Our data suggest that the drive for social upliftment within Africa will be associated with rising levels of obesity, which will require the initiation of targeted sex-specific intervention programmes across specific African communities.

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Conservation of Regional Variation in Sex-Specific Sex Chromosome Regulation.

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Conservation of Regional Variation in Sex-Specific Sex Chromosome Regulation.

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