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首页> 外文期刊>Cell Research >Identification of two distinct transactivation domains in the pluripotency sustaining factor nanog
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Identification of two distinct transactivation domains in the pluripotency sustaining factor nanog

机译：鉴定多能性维持因子nanog中两个不同的反式激活域

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Nanog is a newly identified homeodomain gene that functions to sustain the pluripotency of embryonic stem cells. However, the molecular mechanism through which nanog regulates stem cell pluripotency remains unknown. Mouse nanog encodes a polypeptide of 305 residues with a divergent homeodomain similar to those in the NK-2 family. The rest of nanog contains no apparent homology to any known proteins characterized so far. It is hypothesized that nanog encodes a transcription factor that regulates stem cell pluripotency by switching on or off target genes. To test this hypothesis, we constructed fusion proteins between nanog and DNA binding domains of the yeast transcription factor Gal4 and tested the transactivation potentials of these constructs. Our data demonstrate that both regions N- and C- terminal to the homeodomain have transcription activities. Despite the fact that it contains no apparent transactivation motifs, the C-terminal domain is about 7 times as active as the N-terminal one. This unique arrangement of dual transactivators may confer nanog the flexibility and specificity to regulate downstream genes critical for both pluripotency and differentiation of stem cells.
机译：Nanog是新近鉴定出的同源结构域基因，其功能是维持胚胎干细胞的多能性。但是，nanog调节干细胞多能性的分子机制仍然未知。小鼠nanog编码305个残基的多肽，具有与NK-2家族相似的同源异域。其余的nanog与迄今已表征的任何已知蛋白质均无明显同源性。假设nanog编码通过打开或关闭靶基因来调节干细胞多能性的转录因子。为了检验该假设，我们在酵母转录因子Gal4的nanog和DNA结合结构域之间构建了融合蛋白，并测试了这些构建体的反式激活潜能。我们的数据表明，同源域的N-和C-末端区域均具有转录活性。尽管事实上它不包含明显的反式激活基元，但C末端结构域的活性是N末端结构域的7倍。双重反式激活子的这种独特排列可以赋予nanog灵活性和特异性，以调节对干细胞的多能性和分化至关重要的下游基因。

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