Sexually dimorphic gene expression emerges with embryonic genome activation and is dynamic throughout development.
Sexually dimorphic gene expression emerges with embryonic genome activation and is dynamic throughout development.
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DOI：
10.1186/s12864-015-1506-4
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发表时间：
2015-04-14
期刊：
影响因子：
4.4
通讯作者：
Holland ML
中科院分区：
文献类型：
--
作者：
Lowe R;Gemma C;Rakyan VK;Holland ML
由于性别决定哺乳动物的发育，了解性二态转录组的性质和发育动力学是很重要的。为了探索这一点，我们从小鼠八细胞胚胎、妊娠晚期和成年肝脏中生成了76个全基因组RNA-seq图谱，以及4个基态多能胚胎（ES）细胞系，我们从中生成了RNA-seq和多个ChIP-seq图谱。我们用先前发表的数据补充了这一点，以产生5个植入前发育、妊娠晚期胎盘和体细胞组织以及多个成人组织的快照，用于综合分析。我们在8细胞胚胎中定义了69个基因的高置信度性别二态性特征。性染色体连锁组件的这个签名是在很大程度上保守的整个植入前的发展和ES细胞，而常染色体的组成部分是更动态的。性别偏见的基因表达反映了激活和抑制组蛋白修饰的富集。八细胞特征在很大程度上与从胎儿肝脏定义的特征不重叠，也不与成人肝脏或分析的其他组织相关。在整个发育过程中，性别二型基因的数量不断增加。我们在成人肝脏中发现了比胎儿肝脏多得多的多态性基因。然而，大约三分之二的胎儿肝脏中发现的二型基因也在成人肝脏中二型。成人肝脏特有的性别偏倚表达差异富集了生长激素反应性。着床前发育中的性二态基因表达是由基于性染色体的转录驱动的，而后期发育的特征是性二态常染色体转录。这项系统的研究确定了小鼠发育过程中三个不同的性别二态性阶段，对了解哺乳动物性别特异性表型和疾病的发育起源具有重要意义。本文的在线版本（doi：10.1186/s12864-015-1506-4）包含补充材料，可供授权用户使用。
As sex determines mammalian development, understanding the nature and developmental dynamics of the sexually dimorphic transcriptome is important. To explore this, we generated 76 genome-wide RNA-seq profiles from mouse eight-cell embryos, late gestation and adult livers, together with 4 ground-state pluripotent embryonic (ES) cell lines from which we generated both RNA-seq and multiple ChIP-seq profiles. We complemented this with previously published data to yield 5 snap-shots of pre-implantation development, late-gestation placenta and somatic tissue and multiple adult tissues for integrative analysis. We define a high-confidence sex-dimorphic signature of 69 genes in eight-cell embryos. Sex-chromosome-linked components of this signature are largely conserved throughout pre-implantation development and in ES cells, whilst the autosomal component is more dynamic. Sex-biased gene expression is reflected by enrichment for activating and repressive histone modifications. The eight-cell signature is largely non-overlapping with that defined from fetal liver, neither was it correlated with adult liver or other tissues analysed. The number of sex-dimorphic genes increases throughout development. We identified many more dimorphic genes in adult compared to fetal liver. However, approximately two thirds of the dimorphic genes identified in fetal liver were also dimorphic in adult liver. Sex-biased expression differences unique to adult liver were enriched for growth hormone-responsiveness. Sexually dimorphic gene expression in pre-implantation development is driven by sex-chromosome based transcription, whilst later development is characterised by sex dimorphic autosomal transcription. This systematic study identifies three distinct phases of sex dimorphism throughout mouse development, and has significant implications for understanding the developmental origins of sex-specific phenotypes and disease in mammals. The online version of this article (doi:10.1186/s12864-015-1506-4) contains supplementary material, which is available to authorized users.
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