Novel Transcriptional Corepressors in C. elegans

线虫中的新型转录辅阻遏物

• 批准号: 386398-2013
• 负责人: Taubert, Stefan
• 金额: $ 2.19万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572948
• 关键词: Novel; Transcriptional; Corepressors; C.; elegans

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.

所有生物的遗传信息都编码在DNA中，但要发挥作用，必须将其从DNA转录成RNA。因此，转录过程在所有生物学中具有根本的重要性。毫不奇怪，转录在空间和时间上受到严格的调控。这确保每个细胞在正确的时刻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。其中一些已被充分研究，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，转录辅助调节因子构成了一个庞大而多样的蛋白质家族，它们执行无数不同的功能。因此，大多数辅助调节因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代表了转录研究的重要目标。 为了研究辅助调节因子，我们使用线虫秀丽隐杆线虫，因为它具有特殊的实验易处理性。我们最近的数据表明，进化上保守的蛋白TAG-260是C.线虫，因为它是这些蠕虫的正常发育和生理稳态所必需的。重要的是，尽管已经在培养细胞中研究了TAG-260的人类亲属，但我们的研究是第一次在活体动物的背景下关注TAG-260，为我们提供了明显的优势。在这里，我们建议通过识别其调控靶点，其相互作用蛋白，并通过表征其分子作用模式来表征TAG-260的功能。因此，这项工作对我们理解多细胞动物的转录调控具有重要意义。由于人类和蠕虫蛋白质之间的密切关系，我们的发现也可能有助于了解人类同源物的功能。