Sexual dimorphism of hepatic gene expression: novel biological role of KRAB zinc finger repressors revealed: Figure 1.

Waxman, David J.; Celenza, John L.

doi:10.1101/gad.1154603

Cited by 32 publications

(20 citation statements)

References 59 publications

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“…Sex differences in the effect of hcpd1 (D3Rat46) and hcpd2 (D4Rat76) on dispersion were scalar, but there were significant male-female differences in dispersion patterns by genotype at D9Mgh2 and D12Rat25. Sex may be the most fundamental contrast in biology (Andersson 1994;Gabory et al 2009); there is widespread sexual dimorphism in gene expression (Waxman and Celenza 2003;Clodfelter et al 2006;Yang et al 2006;Wauthier and Waxman 2008) and intersexual genetic correlation is routinely less than unity (Chippindale et al 2001;Stewart et al 2010;van Doorn 2009). Previous work of ours indicates sex effects on the genetic structure of residuals for operant behavior in rats (Perry et al 2010a) and sex chromosomal-autosomal interaction for thermotolerance in rainbow trout (Perry et al 2003).…”

Section: Discussionmentioning

confidence: 93%

Sex Modifies Genetic Effects on Residual Variance in Urinary Calcium Excretion in Rat (Rattus norvegicus)

et al. 2012

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Conventional genetics assumes common variance among alleles or genetic groups. However, evidence from vertebrate and invertebrate models suggests that residual genotypic variance may itself be under partial genetic control. Such a phenomenon would have great significance: high-variability alleles might confound the detection of "classically" acting genes or scatter predicted evolutionary outcomes among unpredicted trajectories. Of the few works on this phenomenon, many implicate sex in some aspect of its control. We found that female genetic hypercalciuric stone-forming (GHS) rats (Rattus norvegicus) had higher coefficients of variation (CVs) for urinary calcium (CV ¼ 0.14) than GHS males (CV ¼ 0.06), and the reverse in normocalciuric Wistar-Kyoto rats (WKY) (CV ♂ ¼ 0.14; CV ♀ ¼ 0.09), suggesting sex-by-genotype interaction on residual variance. We therefore investigated the effect of sex on absolute-transformed residuals in urinary calcium in an F 2 GHS · WKY mapping cohort. Absolute residuals were associated with genotype at two microsatellites, D3Rat46 (RNO3, 33.9 Mb) and D4Mgh1 (RNO4, 84.8 MB) at Bonferroni thresholds across the entire cohort, and with the microsatellites D3Rat46, D9Mgh2 (RNO9, 84.4 Mb), and D12Rat25 (RNO12, 40.4 Mb) in females (P , 0.05) but not males. In GHS chromosome 1 congenic lines bred onto a WKY genomic background, we found that congenic males had significantly (P , 0.0001) higher CVs for urinary calcium (CV ¼ 0.25) than females (CV ¼ 0.15), supporting the hypothesis of the inheritance of sex-by-genotype interaction on this effect. Our findings suggest that genetic effects on residual variance are sex linked; heritable, sex-specific residuals might have great potential implications for evolution, adaptation, and genetic analysis.

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Section: Discussionmentioning

confidence: 93%

Sex Modifies Genetic Effects on Residual Variance in Urinary Calcium Excretion in Rat (Rattus norvegicus)

et al. 2012

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“…The genetic and transcriptional mechanisms regulating differences between the sexes have intensively been investigated in the liver but dimorphic gene expression has also been reported in mouse kidney, blastocysts, lacrimal gland, and brain [2][3][4][5]. A recent microarray analysis of 23,574 transcripts by Yang et al revealed the extent of sexual dimorphism in gene expression to be much greater than previously recognized.…”

Section: Extent Of Global Sexual Dimorphismmentioning

confidence: 99%

Sexual dimorphism in environmental epigenetic programming

Gabory

Attig

Junien

2009

Molecular and Cellular Endocrinology

249

196

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The phenotype of an individual is the result of complex interactions between genotype and current, past and ancestral environment leading to a lifelong remodelling of our epigenomes. The vast majority of common diseases, including atherosclerosis, diabetes, osteoporosis, asthma, neuropsychological and autoimmune diseases, which often take root in early development, display some degree of sex bias, very marked in some cases. This bias could be explained by the role of sex chromosomes, the different regulatory pathways underlying sexual development of most organs and finally, lifelong fluctuating impact of sex hormones. A substantial proportion of dimorphic genes expression might be under the control of sex-specific epigenetic marks. Environmental factors such as social behaviour, nutrition or chemical compounds can influence, in a gender-related manner, these flexible epigenetic marks during particular spatiotemporal windows of life. Thus, finely tuned developmental program aspects, for each sex, may be more sensitive to specific environmental challenges, particularly during developmental programming and gametogenesis, but also throughout the individual's life under the influence of sex steroid hormones and/or sex chromosomes. An unfavourable programming could thus lead to various defects and different susceptibility to diseases between males and females. Recent studies suggest that this epigenetic programming could be sometimes transmitted to subsequent generations in a sex specific manner and lead to transgenerational effects (TGEs).This review summarizes the current understanding in the field of epigenetic programming and highlights the importance of studying both sexes in epidemiological protocols or dietary interventions both in humans and in experimental animal models.

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“…Indeed, differences in patterns of gene expression are significantly attenuated by removal of the pituitary and by genetic models of GH deficiency or resistance (26,27). Replacement of GH in a male or female pattern is sufficient to induce male- or female-specific patterns of gene expression, with the sex-specific effect determined by the length of the interpulse interval (23,(27)(28)(29)(30). There are several genetic models of GH deficiency or resistance in mice (31)(32)(33)(34)(35).…”

Section: Introductionmentioning

confidence: 99%

Sex differences in thrombosis in mice are mediated by sex-specific growth hormone secretion patterns

Wong¹,

Dukes²,

Levy³

et al. 2008

J. Clin. Invest.

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Sex differences in thrombosis are well described, but their underlying mechanism(s) are not completely understood. Coagulation proteins are synthesized in the liver, and liver gene expression is sex specific and depends on sex differences in growth hormone (GH) secretion -males secrete GH in a pulsatile fashion, while females secrete GH continuously. Accordingly, we tested the hypothesis that sex-specific GH secretion patterns cause sex differences in thrombosis. Male mice were more susceptible to thrombosis than females in the thromboplastin-induced pulmonary embolism model and showed shorter clotting times ex vivo. GH-deficient little (lit) mice were protected from thrombosis, and pulsatile GH given to lit mice restored the male clotting phenotype. Moreover, pulsatile GH administration resulted in a male clotting phenotype in control female mice, while continuous GH caused a female clotting phenotype in control male mice. Expression of the coagulation inhibitors Proc, Serpinc1, Serpind1, and Serpina5 were strongly modulated by sex-specific GH patterns, and GH modulated resistance to activated protein C. These results reveal what we believe to be a novel mechanism whereby sex-specific GH patterns mediate sex differences in thrombosis through coordinated changes in the expression of coagulation inhibitor genes in the liver.

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Sexual dimorphism of hepatic gene expression: novel biological role of KRAB zinc finger repressors revealed: Figure 1.

Cited by 32 publications

References 59 publications

Sex Modifies Genetic Effects on Residual Variance in Urinary Calcium Excretion in Rat (Rattus norvegicus)

Sex Modifies Genetic Effects on Residual Variance in Urinary Calcium Excretion in Rat (Rattus norvegicus)

Sexual dimorphism in environmental epigenetic programming

Sex differences in thrombosis in mice are mediated by sex-specific growth hormone secretion patterns

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