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Abstract：
The universal nine-amino-acid transactivation domains (9aaTADs) have been identified in numerous transcription activators. Here, we identified the conserved 9aaTAD motif in all nine members of the specificity protein (SP) family. Previously, the Sp1 transcription factor has been defined as a glutamine-rich activator. We showed by amino acid substitutions that the glutamine residues are completely dispensable for 9aaTAD function and are not conserved in the SP family. We described the origin and evolutionary history of 9aaTADs. The 9aaTADs of the ancestral Sp2 gene became inactivated in early chordates. We next discovered that an accumulation of valines in 9aaTADs inactivated their transactivation function and enabled their strict conservation during evolution. Subsequently, in chordates, Sp2 has duplicated and created new paralogs, Sp1, Sp3, and Sp4 (the SP1-4 clade). During chordate evolution, the dormancy of the Sp2 activation domain lasted over 100 million years. The dormant but still intact ancestral Sp2 activation domains allowed diversification of the SP1-4 clade into activators and repressors. By valine substitution in the 9aaTADs, Sp1 and Sp3 regained their original activator function found in ancestral lower metazoan sea sponges. Therefore, the vertebrate SP1-4 clade could include both repressors and activators. Furthermore, we identified secondary 9aaTADs in Sp2 introns present from fish to primates, including humans. In the gibbon genome, introns containing 9aaTADs were used as exons, which turned the Sp2 gene into an activator. Similarly, we identified introns containing 9aaTADs used conditionally as exons in the (SP family-unrelated) transcription factor SREBP1, suggesting that the intron-9aaTAD reservoir is a general phenomenon.
摘要：
已经在许多转录激活子中鉴定了通用的九氨基酸反式激活结构域(9aaTAD)。这里,我们在特异性蛋白（SP）家族的所有9个成员中鉴定了保守的9aaTAD基序。以前,Sp1转录因子已被定义为富含谷氨酰胺的激活剂。我们通过氨基酸取代表明，谷氨酰胺残基对于9aaTAD功能是完全可有可无的，并且在SP家族中不保守。我们描述了9aaTADs的起源和进化史。祖先Sp2基因的9aaTADs在早期的脊索中失活。我们接下来发现，9aaTAD中缬氨酸的积累使它们的反式激活功能失活，并在进化过程中实现了严格的保守。随后，在脊索中，Sp2已经复制并创建了新的旁系物，Sp1、Sp3和Sp4（SP1-4进化枝）。在脊索动物进化过程中，Sp2激活域的休眠持续了1亿年。休眠但仍完整的祖先Sp2激活域允许SP1-4进化枝多样化为激活子和阻遏物。通过9aaTAD中的缬氨酸取代，Sp1和Sp3恢复了在祖先下部后生动物海海绵中发现的原始激活剂功能。因此,脊椎动物SP1-4进化枝可以包括抑制因子和激活剂。此外，我们确定了从鱼类到灵长类动物的Sp2内含子中的次级9aaTADs，包括人类。在长臂猿基因组中，含有9aaTAD的内含子被用作外显子，将Sp2基因变成激活剂.同样，我们确定了包含9aaTAD的内含子，在（SP家族无关）转录因子SREBP1中有条件地用作外显子，这表明内含子-9aaTAD库是一种普遍现象。
