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首页> 外文期刊>Mechanisms of Development >An ENU-induced point mutation in the mouse Btaf1 gene causes post-gastrulation embryonic lethality and protein instability
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An ENU-induced point mutation in the mouse Btaf1 gene causes post-gastrulation embryonic lethality and protein instability

机译：小鼠Btaf1基因中ENU诱导的点突变导致胎后胚胎致死率和蛋白不稳定

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The mouse Btaf1 gene, an ortholog of yeast MOT1, encodes a highly conserved general transcription factor. The function of this SNF2-like ATPase has been studied mainly in yeast and human cells, which has revealed that it binds directly to TBP, forming the B-TFIID complex. This complex binds to core promoters of RNA polymerase II-transcribed genes and, of crucial importance, BTAF1-TBP interactions have been shown to affect the kinetics of TBP-promoter interactions. Here we report the isolation of a mouse line carrying a Btaf1 allele containing an ENU-induced point mutation that causes a substitution mutation in the BTAF1 ATPase domain. Embryos homozygous for this loss-of-function mutation appear to be morphologically normal until early somite stages, but die between embryonic days 9 and 10.5 displaying growth arrest and edema. Analyses in vitro suggest that the altered protein is less stable and, independent from this, functionally impaired in releasing of TBP from chromatin, but not in binding to TBP
机译：小鼠Btaf1基因是酵母MOT1的直系同源基因，编码高度保守的通用转录因子。主要在酵母和人类细胞中研究了这种SNF2样ATPase的功能，这表明它直接与TBP结合，形成B-TFIID复合物。该复合物与RNA聚合酶II转录基因的核心启动子结合，并且至关重要的是，已显示BTAF1-TBP相互作用会影响TBP-启动子相互作用的动力学。在这里，我们报告了带有Btaf1等位基因的小鼠系的分离，该等位基因包含ENU诱导的点突变，该点突变在BTAF1 ATPase域中引起取代突变。这种功能丧失突变的纯合子在形态上是正常的，直到早期的体节期，但在胚胎的第9天和第10.5天之间死亡，表现出生长停滞和水肿。体外分析表明，改变的蛋白质稳定性较差，并且独立于此而在从染色质释放TBP的功能受损，但不与TBP结合

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