EVOLUTIONARY CONSERVATION OF POSSIBLE FUNCTIONAL DOMAINS OF THE HUMAN AND MURINE XIST GENES
EVOLUTIONARY CONSERVATION OF POSSIBLE FUNCTIONAL DOMAINS OF THE HUMAN AND MURINE XIST GENES
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DOI：
10.1093/hmg/2.6.663
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发表时间：
1993-06-01
影响因子：
3.5
通讯作者：
WILLARD, HF
中科院分区：
文献类型：
--
作者：
HENDRICH, BD;BROWN, CJ;WILLARD, HF
人类XIST基因，一个在X染色体失活中起作用的候选基因，最近被克隆并测序，得到了一个17kb的cDNA，没有明显的显著的，保守的开放阅读框。此外，通过RNA原位杂交，XIST转录本已在细胞核内定位到Barr小体。这种亚核定位和缺乏任何重要的蛋白质编码潜力表明，XIST可能在细胞核内作为一种功能性RNA。在缺乏保守的开放阅读框的情况下，我们将进化研究作为阐明XIST在X失活过程中的功能的第一步。虽然XIST探针在许多真动物中检测到同源物，但序列比较需要显著的间隙，并揭示其他基因中编码区和非编码区之间的身份水平。此外，在几种灵长类动物中，最可能的候选开放阅读框的序列比较揭示了通常与蛋白质编码区无关的序列变化。然而，XIST的其他特征在不同物种中是保守的，包括主要转录起始位点的位置和基因5'端活跃的X染色体特异性DNA甲基化模式。最后，通过比较携带不同Xce等位基因的小鼠菌株的Xist保守5'重复序列，探讨了小鼠Xce等位基因对X失活倾向不同的分子基础。
The human XIST gene, a candidate for a role in X chromosome inactivation, has recently been cloned and sequenced, yielding a 17 kb cDNA with no apparent significant, conserved open reading frame. In addition, the XIST transcript has been localized within the nucleus to the Barr body by RNA in situ hybridization. This subnuclear localization and lack of any significant protein-coding potential suggest that XIST may act as a functional RNA within the nucleus. In the absence of a conserved open reading frame, we have turned to evolutionary studies as a first step toward elucidating a function for XIST in the process of X inactivation. While probes for XIST detect homologues in numerous eutherians, sequence comparisons require significant gapping and reveal identity levels intermediate between those seen for coding and non-coding regions in other genes. Further, sequence comparison of the most likely candidate open reading frame among several primate species reveals sequence changes not normally associated with protein-coding regions. Other features of XIST are conserved in different species, however, including the position of a major transcription start site and active X chromosome-specific DNA methylation patterns at the gene's 5' end. Finally, a possible molecular basis for differing propensity toward X inactivation between Xce alleles in mouse is investigated by comparing the sequence of the Xist conserved 5' repeats in mouse strains carrying different Xce alleles.