Novel Transcriptional Corepressors in C. elegans

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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.