<i>Sry</i>, more than testis determination?

Turner, Monte E.; Ely, Daniel; Prokop, Jeremy W.; Milsted, Amy

doi:10.1152/ajpregu.00645.2010

Cited by 45 publications

(38 citation statements)

References 108 publications

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“…Because Sry sequences, except those for HMG boxes, are poorly conserved among species, and Sry genes other than mouse do not possess a CAG-repeat stretch, it is impossible to directly apply the results from mouse studies to other mammalian species [18]. Nevertheless, Sry has been recently described to play roles other than testis determination [19]. An association between the Y chromosome and blood pressure has been repeatedly reported in rats and humans [3,20-24], and Sry is thought to be the most promising candidate for the Y chromosomal effect [23].…”

Section: Resultsmentioning

confidence: 99%

Effect of the Y chromosome on plasma high-density lipoprotein-cholesterol levels in Y-chromosome-consomic mouse strains

Suto

Satou

2014

BMC Res Notes

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BackgroundPlasma high-density lipoprotein (HDL)-cholesterol level is a clinically important quantitative phenotype that widely varies among inbred mouse strains. Several genes or loci associated with plasma HDL-cholesterol levels have been identified on autosomes and the X chromosome. In contrast, genes or loci on the Y chromosome have not attracted significant attention hitherto. Therefore, we investigated the effects of the Y chromosome on plasma HDL-cholesterol levels in Y- chromosome-consomic (Y-consomic) mouse strains.FindingsPlasma HDL-cholesterol level data from 16 Y-consomic strains demonstrated that the Y chromosome substitutions significantly altered plasma HDL-cholesterol levels, i.e., variations in the plasma HDL-cholesterol level could be partially explained by Y chromosome genes. We obtained the following results from the genotype data on 30 single nucleotide polymorphisms (SNPs), including nonsynonymous and synonymous SNPs and 9 polymorphisms in Sry: (1) Variation in rs46947134 of Uty was significantly associated with plasma HDL-cholesterol levels. (2) A CAG repeat number polymorphism in Sry was significantly associated with plasma HDL-cholesterol levels. (3) Strains with a certain haplotype of the Mus musculus domesticus-type Y chromosome had significantly lower plasma HDL-cholesterol levels than strains with a certain haplotype of the M. m. musculus-type Y chromosome.ConclusionsThe effect of the Y chromosome on plasma HDL-cholesterol levels was confirmed in the Y-consomic strains. We identified several variants associated with plasma HDL-cholesterol levels. Because the physiological significance of various Y-linked genes remains unclear, the results of this study will provide further insights into the functions of Y-linked genes in lipid metabolism.

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Section: Resultsmentioning

confidence: 99%

Effect of the Y chromosome on plasma high-density lipoprotein-cholesterol levels in Y-chromosome-consomic mouse strains

Suto

Satou

2014

BMC Res Notes

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“…The effects of sex chromosome genes acting outside of the gonads is also an important contributor to sex differences. Both X and Y genes, which are differentially present in each XX vs. XY cell, act in a sex-biased manner to cause sex differences in nongonadal phenotypes (32,33). In fact, the genetic sex difference leads to clear sex bias in the genome: Y genes act only in XY cells, X genes escaping X-inactivation may be expressed constitutively higher in XX than XY cells, XX cells receive both a paternal and maternal imprint on X chromosomes whereas XY cells receive only a maternal imprint, and X or Y chromosomes harbor segments of sex-specific heterochromatin that may alter the epigenetic status of autosomes in a sex-specific manner.…”

Section: Discussionmentioning

confidence: 99%

IUGR prevents IGF-1 upregulation in juvenile male mice by perturbing postnatal IGF-1 chromatin remodeling

Fung

Yang

et al. 2015

Pediatr Res

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Background: Intrauterine growth restriction (IUGR) offspring with rapid catch-up growth are at increased risk for early obesity especially in males. Persistent insulin-like growth factor-1 (IGF-1) reduction is an important risk factor. Using a mouse model of maternal hypertension-induced IUGR, we examined IGF-1 levels, promoter DNA methylation, and histone H3 covalent modifications at birth (D1). We additionally investigated whether prenatal perturbations could reset at preadolescence (D21). Methods: IUGR was induced via maternal thromboxane A 2 -analog infusion in mice. results: IUGR uniformly decreased D1 IGF-1 mRNA and protein levels with reduced promoter 1 (P1) transcription and increased P1 DNA methylation. IUGR males also had increased H3K4ac at exon 5 and 3′ distal UTR. At D21, IUGR males continued to have decreased IGF-1 levels, originating from both P1 and P2 with reduced 1A variant. IUGR males also had decreased activation mark of H3K4me3 at P1 compared with sham males. In contrast, D21 IUGR females normalized their IGF-1 levels, in association with an increased activation mark of H3K4me3 at P1 compared with sham females. conclusion: IUGR uniformly affected D1 hepatic IGF-1 epigenetic modifications in both sexes. However, at preadolescence, IUGR males are unable to correct for the prenatal reduction possibly due to a more perturbed IGF-1 chromatin structure.i ntrauterine growth restriction (IUGR) predisposes offspring toward early-onset metabolic syndrome. This predisposition is particularly pertinent with rapid postnatal catch-up growth and affects males more than females (1). The molecular mechanisms underlying this sex-specific predisposition remain elusive. Insulin-like growth factor 1 (IGF-1), a major regulator of growth and metabolism, has generated significant interest in the field (2). IGF-1 disruption has been implicated in aberrant growth and development of metabolic syndrome in both IUGR humans and animal models (3-6). In particular, decreased IGF-1 have been observed in IUGR humans who ultimately develop metabolic syndrome as adults (7,8).The IGF-1 gene is an ideal candidate to examine IUGR's effects not only because of its growth and metabolic properties but because of its complex gene structure allowing for developmental-and tissue-specific expression. The majority of serum IGF-1 is synthesized from the liver (9). The IGF-1 gene is regulated by two alternative promoters, promoter P1 initiates transcription from exon 1 while promoter P2 from exon 2. P1 is active in fetal life, whereas P2 becomes upregulated at ~3 wk of life when growth hormone exerts its effects on the rodent IGF-1 gene (10). The rodent IGF-1 gene also has an alternatively spliced exon, with the A variant excluding exon 5 and the B variant includes exon 5. Both alternative promoter selection and alternative exon splicing require specific epigenetic modifications to direct transcriptional machinery for specific mRNA transcript generation (11,12).Given that prenatal insults are known to affect gene-specific DNA methylation a...

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“…In many of these same tissues, the male specific gene Sry is expressed in the rat [33]. The Sry gene has been shown to contribute to the elevation of blood pressure in the SHR [34] partially through its regulation of the RAS, producing increased Ang II levels [35,36], and through its role in the sympathetic nervous system [37].…”

Section: Discussionmentioning

confidence: 99%

MAS promoter regulation: a role for Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism

et al. 2014

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The ACE2/Ang-(1-7)/MAS axis of the renin-angiotensin system has emerged as a pathway of interest in treating both cardiovascular disorders and cancer. The MAS protein is known to bind to and be activated by Ang-(1-7); however mechanisms of this activation are just starting to be understood. Whereas there are strong biochemical data regarding regulation and activation of the AT1 and AT2 receptors, with models of how Ang II binds each receptor, fewer studies have characterized MAS. We characterize the MAS promoter and provide a potential feedback mechanism that would compensate for the MAS degradation following activation by Ang-(1-7). Analysis of ENCODE data for the MAS promoter revealed potential epigenetic control by KRAB/KAP1. A proximal promoter construct for the MAS gene was repressed by the SOX proteins SRY, SOX2, SOX3, and SOX14, of which SRY is known to interact with the KRAB domain. The proteins KRAB/KAP1 can both be tyrosine nitrated, causing the dissociation of the KAP-1 protein, and thus a potential loss of epigenetic control. Activation of MAS can lead to an increase in nitric oxide, suggesting feedback mechanisms of MAS on its own promoter. These results present a more complete view of MAS regulation and for the first time suggest biochemical outcomes for nitration to the KRAB domain.

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Sry, more than testis determination?

Cited by 45 publications

References 108 publications

Effect of the Y chromosome on plasma high-density lipoprotein-cholesterol levels in Y-chromosome-consomic mouse strains

Effect of the Y chromosome on plasma high-density lipoprotein-cholesterol levels in Y-chromosome-consomic mouse strains

IUGR prevents IGF-1 upregulation in juvenile male mice by perturbing postnatal IGF-1 chromatin remodeling

MAS promoter regulation: a role for Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism

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