Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells.

Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells.
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DOI:
10.1186/s13293-017-0150-x
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发表时间:
2017-08-17
影响因子:
7.9
通讯作者:
Engel N
Engel N
中科院分区:
医学2区
文献类型:
--
作者:
Werner RJ;Schultz BM;Huhn JM;Jelinek J;Madzo J;Engel N

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植入前胚胎在灵长类动物和啮齿类动物中都表现出性别二态性。为了确定这些差异是否反映了性别偏倚的表达模式,我们通过RNA测序生成了6个40,xx, 6个40,xy和2个39,x小鼠胚胎干细胞的转录组谱。我们发现了数百种编码和非编码rna在男性和女性细胞之间的差异表达。令人惊讶的是,其中大多数是常染色体,包括RNA编码转录和表观遗传和染色质重塑因子。我们在男性和女性细胞中发现了不同的Prdm14响应增强子活性,这与Prdm14的性别特异性表达水平相关。这是首次报道胚胎干细胞中的性别特异性增强子活性。对XX系和XY系之间x连锁基因表达模式的评估揭示了四种不同的类型:(1)基因在雌性细胞中表达量高出2倍;(2)一组在女性细胞中表达水平远高于2倍的基因;(3)男性和女性细胞中具有相同RNA水平的基因;引人注目的是,(4)少数基因在XY系中有较高的表达。对常染色体基因表达的进一步评估显示,尽管存在适当的父母起源模式,但印迹位点的表达存在差异。39,x系与XY细胞紧密结合,为人类Turner综合征相关基因的潜在调控提供了见解。此外,包括39,x系允许进行三方比较,描绘X和Y染色体依赖模式。总的来说,我们的研究结果支持性染色体在胚胎发育早期建立性别特异性网络中的作用,并提供了在这些阶段起源的性染色体非整倍体的影响的见解。本文的在线版本(doi:10.1186/s13293-017-0150-x)包含补充材料,可供授权用户使用。
Pre-implantation embryos exhibit sexual dimorphisms in both primates and rodents. To determine whether these differences reflected sex-biased expression patterns, we generated transcriptome profiles for six 40,XX, six 40,XY, and two 39,X mouse embryonic stem (ES) cells by RNA sequencing. We found hundreds of coding and non-coding RNAs that were differentially expressed between male and female cells. Surprisingly, the majority of these were autosomal and included RNA encoding transcription and epigenetic and chromatin remodeling factors. We showed differential Prdm14-responsive enhancer activity in male and female cells, correlating with the sex-specific levels of Prdm14 expression. This is the first time sex-specific enhancer activity in ES cells has been reported. Evaluation of X-linked gene expression patterns between our XX and XY lines revealed four distinct categories: (1) genes showing 2-fold greater expression in the female cells; (2) a set of genes with expression levels well above 2-fold in female cells; (3) genes with equivalent RNA levels in male and female cells; and strikingly, (4) a small number of genes with higher expression in the XY lines. Further evaluation of autosomal gene expression revealed differential expression of imprinted loci, despite appropriate parent-of-origin patterns. The 39,X lines aligned closely with the XY cells and provided insights into potential regulation of genes associated with Turner syndrome in humans. Moreover, inclusion of the 39,X lines permitted three-way comparisons, delineating X and Y chromosome-dependent patterns. Overall, our results support the role of the sex chromosomes in establishing sex-specific networks early in embryonic development and provide insights into effects of sex chromosome aneuploidies originating at those stages. The online version of this article (doi:10.1186/s13293-017-0150-x) contains supplementary material, which is available to authorized users.
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