Tissue-specific expression and regulation of sexually dimorphic genes in mice
Tissue-specific expression and regulation of sexually dimorphic genes in mice
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DOI：
10.1101/gr.5217506
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发表时间：
2006-08-01
期刊：
影响因子：
7
通讯作者：
Lusis, Aldons J.
中科院分区：
文献类型：
--
作者：
Yang, Xia;Schadt, Eric E.;Lusis, Aldons J.
我们报道了334只近交系C57BL/6J和C3H/HeJ杂交小鼠多个体细胞组织中基因表达的性别差异的综合分析。对大量个体的分析提供了检测性别间相对较小的表达差异的能力，并利用交叉杂交分析了性别二态基因表达的遗传控制。对23,574个转录本进行的微阵列分析显示，基因表达的性别二型性程度比之前认识的要大得多。因此，数千个基因在肝脏、脂肪和肌肉中表现出性别二型性，数百个基因在大脑中表现出性别二型性。这些基因表现出高度组织特异性的表达模式，并在基因本体论数据库中代表的不同途径中得到丰富。它们还显示出染色体丰富的证据，不仅在性染色体上，而且在几个常染色体上也是如此。遗传分析提供了性二型基因亚群全球调控的证据，因为大量这些基因的转录水平受几个表现组织特异性控制的表达数量性状基因座(EQTL)热点的控制。此外，在性别二态基因中发现了许多组织特异的转录因子结合位点。
We report a comprehensive analysis of gene expression differences between sexes in multiple somatic tissues of 334 mice derived from an intercross between inbred mouse strains C57BL/6J and C3H/HeJ. The analysis of a large number of individuals provided the power to detect relatively small differences in expression between sexes, and the use of an intercross allowed analysis of the genetic control of sexually dimorphic gene expression. Microarray analysis of 23,574 transcripts revealed that the extent of sexual dimorphism in gene expression was much greater than previously recognized. Thus, thousands of genes showed sexual dimorphism in liver, adipose, and muscle, and hundreds of genes were sexually dimorphic in brain. These genes exhibited highly tissue-specific patterns of expression and were enriched for distinct pathways represented in the Gene Ontology database. They also showed evidence of chromosomal enrichment, not only on the sex chromosomes, but also on several autosomes. Genetic analyses provided evidence of the global regulation of subsets of the sexually dimorphic genes, as the transcript levels of a large number of these genes were controlled by several expression quantitative trait loci (eQTL) hotspots that exhibited tissue-specific control. Moreover, many tissue-specific transcription factor binding sites were found to be enriched in the sexually dimorphic genes.