Heterogeneous gene expression from the inactive X chromosome: An X-linked gene that escapes X inactivation in some human cell lines but is inactivated in others
Heterogeneous gene expression from the inactive X chromosome: An X-linked gene that escapes X inactivation in some human cell lines but is inactivated in others
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DOI：
10.1073/pnas.96.13.7364
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发表时间：
1999-06-22
影响因子：
11.1
通讯作者：
Willard, HF
中科院分区：
文献类型：
--
作者：
Carrel, L;Willard, HF
在哺乳动物雌性中，由于X染色体失活，一条X染色体上的大多数基因在转录上沉默。虽然已经确定一些X连锁基因“逃脱”了X染色体失活，并在活性（Xa）和非活性（Xi） X染色体上表达，但大多数X连锁基因表达的染色体控制模型都假设给定基因的X失活状态在种群中的不同雌性中是恒定的。在本报告中，我们通过转录多态性检测了人类s连锁基因在完全非随机X失活的雌性原代细胞系中的表达，通过区分Sa和Si的表达，用于记录该检测系统的6个X连锁基因在所有信息细胞系中显示为单等位基因表达，与X失活一致，然而，观察到另一个基因REP1的新表达模式；在一些品系中检测到单等位基因表达（表明失活），而在其他品系中检测到双等位基因表达（表明逃避失活）。此外，在表达REP1的细胞系中，Si的表达水平也有所不同。通过单细胞的表达试验，研究了Si表达的细胞基础。这些数据表明，REP1在所有细胞中都从Xi中表达，但相对于Sa水平的表达水平降低。这些发现表明，Si基因的表达处于先前未被怀疑的遗传或表观遗传控制水平下，可能涉及染色质组织的局部或区域变化，这些变化决定了基因是否逃逸或受到X失活的影响。
In mammalian females, most genes on one X chromosome are transcriptionally silenced as a result of X chromosome inactivation, Whereas it is well established that some X-linked genes "escape'' X inactivation and are expressed from both active (Xa) and inactive (Xi) X chromosomes, most models for the chromosomal control of X-linked gene expression assume that the X inactivation status of a given gene is constant among different females within a population. In this report, we test the expression of human S-linked genes in primary cell lines from females with complete nonrandom X inactivation by using transcribed polymorphisms to distinguish Sa and Si expression, Six X-linked genes used to document this assay system show ed monoallelic expression in all informative cell lines, consistent with X inactivation, However, a novel pattern of expression was observed for another gene, REP1; monoallelic expression, indicating inactivation, was detected in some lines, whereas biallelic expression, indicating escape from inactivation, H-as detected in others. Furthermore, levels of Si expression,varied among cell lines that expressed REP1, The cellular basis of Si expression uas examined by expression assays in single cells. These data indicate that REP1 is expressed from the Xi in all cells, but that the level of expression relative to Sa levels is reduced. These findings suggest that Si gene expression is under a previously unsuspected level of genetic or epigenetic control, likely involving local or regional changes in chromatin organization that determine whether a gene escapes or is subject to X inactivation.