Global survey of escape from X inactivation by RNA-sequencing in mouse
Global survey of escape from X inactivation by RNA-sequencing in mouse
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DOI：
10.1101/gr.103200.109
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发表时间：
2010-05-01
期刊：
影响因子：
7
通讯作者：
Disteche, Christine M.
中科院分区：
文献类型：
--
作者：
Yang, Fan;Babak, Tomas;Disteche, Christine M.
X染色体失活使两性之间的基因表达量相等，但有些基因逃避沉默，因此在雌性中从两个等位基因表达。为了调查小鼠中的X失活和逃逸，我们在具有完全偏斜的X失活的Mus musculus x Mus spretus细胞中进行RNA测序，依靠单核苷酸多态性的表达来区分等位基因来源。393个小鼠基因中有13个（3.3%）在失活X中有显著表达，其中包括8个新的逃逸基因。我们估计，与人类相比，小鼠的逃避基因明显较少。此外，逃逸基因在小鼠中没有聚集，不像人类中的大逃逸结构域，这表明表达在单个基因水平上受到控制。我们的研究结果与雌性小鼠和具有单个X染色体的女性之间表型的显著差异相一致-小鼠中接近正常的表型与特纳综合征和人类中的多种异常。我们发现逃逸基因的特点是组蛋白H3的赖氨酸27没有三甲基化，这是一种与X失活基因相关的染色质修饰。此外，这种表观遗传标记对一些小鼠基因具有发育调控作用。
X inactivation equalizes the dosage of gene expression between the sexes, but some genes escape silencing and are thus expressed from both alleles in females. To survey X inactivation and escape in mouse, we performed RNA sequencing in Mus musculus x Mus spretus cells with complete skewing of X inactivation, relying on expression of single nucleotide polymorphisms to discriminate allelic origin. Thirteen of 393 (3.3%) mouse genes had significant expression from the inactive X, including eight novel escape genes. We estimate that mice have significantly fewer escape genes compared with humans. Furthermore, escape genes did not cluster in mouse, unlike the large escape domains in human, suggesting that expression is controlled at the level of individual genes. Our findings are consistent with the striking differences in phenotypes between female mice and women with a single X chromosome-a near normal phenotype in mice versus Turner syndrome and multiple abnormalities in humans. We found that escape genes are marked by the absence of trimethylation at lysine 27 of histone H3, a chromatin modification associated with genes subject to X inactivation. Furthermore, this epigenetic mark is developmentally regulated for some mouse genes.