Novel Transcriptional Corepressors in C. elegans

所有生物的遗传信息都编码在它们的DNA中，但要有用，它必须从DNA转录成RNA。因此，转录过程在所有生物学中都是至关重要的。毫不奇怪，转录在空间和时间上都受到严格的监管。这确保了每个细胞在正确的时间利用适当的遗传信息。几个参与者合作以确保适当的基因转录。其中一些已经得到了很好的研究，并以典型的分子方式发挥作用；例如，所谓的转录因子与DNA元件结合，然后激活或抑制附近的转录。相比之下，转录共调节因子构成了一个庞大而多样的蛋白质家族，它们执行着无数不同的功能。因此，大多数协调控子的生物学作用仍然知之甚少。因此，它们在活体动物中的详细研究是转录研究的一个重要目标。为了研究协同调节因子，我们使用线虫秀丽线虫，因为它具有特殊的实验可控性。我们最近的数据表明，进化上保守的蛋白Tag-260是线虫的重要辅助调节因子，因为它是线虫正常发育和生理动态平衡所必需的。重要的是，尽管TAG-260的人类近亲已经在培养细胞中进行了研究，但我们的研究是第一次在活体动物的背景下关注TAG-260，这为我们提供了一个明显的优势。在这里，我们建议通过确定其调控目标、其相互作用的蛋白质以及通过表征其分子作用模式来表征TAG-260的功能。因此，这项工作对于我们理解多细胞动物的转录调控具有重要的意义。由于人类和蠕虫蛋白之间的密切关系，我们的发现也可能有助于深入了解人类同源物的功能。

All organisms' genetic information is encoded in their DNA, but to be useful it must be transcribed from DNA into RNA. The process of transcription is therefore of fundamental importance in all biology. Not surprisingly, transcription is subject to tight regulation in space and time. This ensures that each cell utilizes the appropriate genetic information at the right moment. Several players cooperate to ensure appropriate gene transcription. Some of these are well studied and act in a typical molecular fashion; for example, the so-called transcription factors bind to DNA elements and then either activate of repress nearby transcription. In contrast, transcriptional coregulators constitute a large and diverse family of proteins that perform a myriad of different functions. Accordingly, the biological roles of most coregulators remain poorly understood. Therefore, their detailed investigation in live animals represents an important goal in transcription research. To study coregulators, we use the nematode worm Caenorhabditis elegans, because it features exceptional experimental tractability. Our recent data demonstrate that the evolutionarily conserved protein TAG-260 is an important coregulator in C. elegans, as it is required for normal development and for physiological homeostasis in these worms. Importantly, although the human relatives of TAG-260 have been studied in cultured cells, our study is the first to focus on TAG-260 in the context of live animals, providing us with a distinct advantage. Here, we propose to characterize TAG-260 functionally by identifying its regulatory targets, its interacting proteins, and by characterizing its molecular mode of action. Thus, this work has important implications for our understanding of transcriptional regulation in multi-cellular animals. Because of the close relationship between the human and worm proteins, our findings may also yield insight into how the human homologues function.