Female mice lacking Xist RNA show partial dosage compensation and survive to term.
Female mice lacking Xist RNA show partial dosage compensation and survive to term.
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DOI：
10.1101/gad.281162.116
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发表时间：
2016-08-01
影响因子：
10.5
通讯作者：
Lee JT
中科院分区：
文献类型：
--
作者：
Yang L;Kirby JE;Sunwoo H;Lee JT
在这项研究中，Yang等人表明，缺乏X染色体失活所需的Xist RNA的小鼠可以正常发育并存活至足月;然而，Xist基因缺失的小鼠在成年前死亡。这项研究提供了新的见解Xist独立的剂量补偿机制，并表明，从X-常染色体平衡的小偏差可以对整体健身产生深远的影响。X染色体失活（XCI）补偿了雄性和雌性哺乳动物之间X染色体数目的差异。XCI由Xist RNA协调，其在早期发育中的表达导致女性中一条X染色体的转录沉默。敲除研究已经建立了Xist与从父亲遗传Xist缺失的雌性胚胎的不存活的要求。在这里，我们报告说，缺乏Xist RNA的雌性小鼠可以令人惊讶地发育并存活到足月。无xist基因的雌性出生频率较低，出生时体型较小，但器官形成基本正常。转录组学分析表明，在多种组织中有数百个X连锁基因显著过表达。因此，尽管缺乏剂量补偿，Xist基因敲除小鼠仍能发育至足月。然而，X-常染色体剂量失衡的程度低于预期（1.14倍至1.36倍）。因此，部分剂量补偿可以在没有Xist的情况下实现，支持固有基因组平衡的想法。然而，到目前为止，没有一个突变小鼠存活超过断奶阶段。猝死与出生后器官成熟失败有关。我们的数据表明，XIST独立的剂量补偿机制，并表明，从X-常染色体平衡的小偏差可以对整体健身产生深远的影响。
In this study, Yang et al. show that mice lacking Xist RNA, which is needed for X-chromosome inactivation, can develop normally and survive to term; however, Xist-null mice die before adulthood. This study provides new insight into Xist-independent mechanisms of dosage compensation and demonstrates that small deviations from X-autosomal balance can have profound effects on overall fitness. X-chromosome inactivation (XCI) compensates for differences in X-chromosome number between male and female mammals. XCI is orchestrated by Xist RNA, whose expression in early development leads to transcriptional silencing of one X chromosome in the female. Knockout studies have established a requirement for Xist with inviability of female embryos that inherit an Xist deletion from the father. Here, we report that female mice lacking Xist RNA can, surprisingly, develop and survive to term. Xist-null females are born at lower frequency and are smaller at birth, but organogenesis is mostly normal. Transcriptomic analysis indicates significant overexpression of hundreds of X-linked genes across multiple tissues. Therefore, Xist-null mice can develop to term in spite of a deficiency of dosage compensation. However, the degree of X-autosomal dosage imbalance was less than anticipated (1.14-fold to 1.36-fold). Thus, partial dosage compensation can be achieved without Xist, supporting the idea of inherent genome balance. Nevertheless, to date, none of the mutant mice has survived beyond weaning stage. Sudden death is associated with failure of postnatal organ maturation. Our data suggest Xist-independent mechanisms of dosage compensation and demonstrate that small deviations from X-autosomal balance can have profound effects on overall fitness.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
小鼠中的剂量补偿平衡了X连锁基因的上调和沉默。
影响因子：
9.8
作者：
Lin, Hong;Gupta, Vibhor;Vermilyea, Matthew D;Falciani, Francesco;Lee, Jeannie T;O'Neill, Laura P;Turner, Bryan M
通讯作者：
Turner, Bryan M
影响因子：
2.6
作者：
Hayashi, Shigemi;Lewis, Paula;McMahon, Andrew P.
通讯作者：
McMahon, Andrew P.
影响因子：
64.5
作者：
Alkass, Kanar;Panula, Joni;Bergmann, Olaf
通讯作者：
Bergmann, Olaf
DOI：
10.1126/science.1237973
发表时间：
2013-08-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Engreitz JM;Pandya-Jones A;McDonel P;Shishkin A;Sirokman K;Surka C;Kadri S;Xing J;Goren A;Lander ES;Plath K;Guttman M
通讯作者：
Guttman M