Grant: Operating Grant

The regulated expression of human genes determines the developmental fates of human cells, and aberrations in this process can lead to cancer and many other diseases. As well, the use of transcription factors to change the developmental fates of human cells underpins important recent progress in regenerative medicine. The transcription of human genes is controlled by about 1600 distinct transcription factors, which are proteins that recognize specific DNA sequences in the vicinities of the genes whose expression they control. A great deal of effort has been devoted to deciphering the DNA sequences recognized by transcription factors and identifying the DNA sites that they bind to in human cells. However, the complexity of human gene regulation is achieved by groups of these transcription factors working together to recruit components of the transcription machinery to particular genes. We propose to identify which of the human transcription factors interact with each other and which of the many components of the human transcriptional machinery are targeted by each of these transcription factors. Understanding how human transcription factors collaborate with each other to regulate human gene expression promises to facilitate the future development of regenerative medicine and the future development of drugs that target gene expression to treat human disease.