Activity map of the tammar X chromosome shows that marsupial X inactivation is incomplete and escape is stochastic

Activity map of the tammar X chromosome shows that marsupial X inactivation is incomplete and escape is stochastic
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DOI:
10.1186/gb-2010-11-12-r122
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发表时间:
2010-01-01
期刊:
影响因子:
12.3
通讯作者:
Graves, Jennifer A. M.
Graves, Jennifer A. M.
中科院分区:
生物学1区
文献类型:
--
作者:
Al Nadaf, Shafagh;Waters, Paul D.;Graves, Jennifer A. M.

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背景:X染色体失活是表观遗传沉默的一个引人注目的例子。为了推断这个复杂的系统是如何演变的,我们研究了X失活的模式有袋动物,tammar小袋鼠(Macropus eugenii)。在有袋类动物中,X失活是已知的父系,不完整和组织特异性,并发生在没有XIST orthologue.Results:我们研究了使用定量PCR的X-传播的基因的表达,揭示了不同位点的剂量补偿范围。为了评估1X或2X活性成纤维细胞的频率,我们使用RNA-FISH在细胞水平上研究了32个X携带基因的表达。在雌性成纤维细胞中,双色RNA-FISH显示基因从两个位点失活的细胞核中的同一个X(活性X)协调表达。然而,其他X上的基因座独立地逃避失活,每个基因座显示出1X活性和2X活性核的特征频率,相当于随机逃避。我们构建了一个活动图的tammar小袋鼠不活跃的X染色体,其中确定没有基因的位置和失活的程度之间的关系,也没有任何相关性与存在或不存在的Y-borne paradigm.Conclusions:在tammar小袋鼠,一个X(假定是母亲)是在所有的细胞中表达,但基因上的其他(父亲)X逃脱失活独立和特征频率。有袋类的父源性和不完全的X染色体失活,伴随着随机逃逸,似乎与真兽目的X染色体失活过程截然不同。我们没有发现从一个X失活中心的失活极性传播的证据。
Background: X chromosome inactivation is a spectacular example of epigenetic silencing. In order to deduce how this complex system evolved, we examined X inactivation in a model marsupial, the tammar wallaby (Macropus eugenii). In marsupials, X inactivation is known to be paternal, incomplete and tissue-specific, and occurs in the absence of an XIST orthologue.Results: We examined expression of X-borne genes using quantitative PCR, revealing a range of dosage compensation for different loci. To assess the frequency of 1X- or 2X-active fibroblasts, we investigated expression of 32 X-borne genes at the cellular level using RNA-FISH. In female fibroblasts, two-color RNA-FISH showed that genes were coordinately expressed from the same X (active X) in nuclei in which both loci were inactivated. However, loci on the other X escape inactivation independently, with each locus showing a characteristic frequency of 1X-active and 2X-active nuclei, equivalent to stochastic escape. We constructed an activity map of the tammar wallaby inactive X chromosome, which identified no relationship between gene location and extent of inactivation, nor any correlation with the presence or absence of a Y-borne paralog.Conclusions: In the tammar wallaby, one X (presumed to be maternal) is expressed in all cells, but genes on the other (paternal) X escape inactivation independently and at characteristic frequencies. The paternal and incomplete X chromosome inactivation in marsupials, with stochastic escape, appears to be quite distinct from the X chromosome inactivation process in eutherians. We find no evidence for a polar spread of inactivation from an X inactivation center.