Inactivation status of PCDH11X:: sexual dimorphisms in gene expression levels in brain
Inactivation status of PCDH11X:: sexual dimorphisms in gene expression levels in brain
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DOI：
10.1007/s00439-006-0134-0
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发表时间：
2006-04-01
期刊：
影响因子：
5.3
通讯作者：
Crow, TJ
中科院分区：
文献类型：
--
作者：
Lopes, AM;Ross, N;Crow, TJ
逃避X染色体失活的基因被预测为导致性别间基因剂量差异的原因，并且是参与X染色体非整倍体个体观察到的表型的主要候选基因。特别令人感兴趣的是原钙粘蛋白X(PCDH11X或PCDHX)，这是最近在大脑中表达的一种基因。在人类中，PCDH11X在Y染色体上有同源基因，并被预测可以逃脱X-失活。通过亚硫酸氢盐测序分析，我们发现在活动和非活动的X染色体上都没有CpG岛甲基化，这提供了一个强有力的迹象，表明PCDH11X在人类中逃脱了失活。此外，通过实时定量聚合酶链式反应观察到脑组织中PCDH11X表达水平的性别二型性，女性PCDH11X转录本的丰度高达2倍。我们将这些发现与人脑中的性别二型性特征联系起来。有趣的是，PCDH11X/Y基因对是智人独有的，因为X连锁基因在人类和黑猩猩血统分裂后被转位到Y染色体上。尽管在人类和黑猩猩之间没有发现启动子甲基化的差异，但人类PCDH11X上调的证据值得进一步研究。
Genes escaping X-inactivation are predicted to contribute to differences in gene dosage between the sexes and are the prime candidates for being involved in the phenotype observed in individuals with X chromosome aneuploidies. Of particular interest is ProtocadherinX (PCDH11X or PCDHX), a recently described gene expressed in brain. In humans, PCDH11X has a homologue on the Y chromosome and is predicted to escape from X-inactivation. Employing bisulphite sequencing analysis we found absence of CpG island methylation on both the active and the inactive X chromosomes, providing a strong indication that PCDH11X escapes inactivation in humans. Furthermore, a sexual dimorphism in levels of expression in brain tissue was observed by quantitative real-time PCR, with females presenting an up to 2-fold excess in the abundance of PCDH11X transcripts. We relate these findings to sexually dimorphic traits in the human brain. Interestingly, PCDH11X/Y gene pair is unique to Homo sapiens, since the X-linked gene was transposed to the Y chromosome after the human-chimpanzee lineages split. Although no differences in promoter methylation were found between humans and chimpanzees, evidence of an upregulation of PCDH11X in humans deserves further investigation.