The transcriptional regulatory network that controls the mammalian cell cycle is important for understanding complex processes like embryonic development and tissue differentiation, and an improved understanding of this regulatory network should lead to deeper understanding of the altered processes that occur in cancer cells. Several transcriptional regulators that are likely regulators of the human cell cycle have been identified. These include members of the E2F family, human Forkhead proteins (FKHR and FKHRL1), Serum Responsive Factor (SRF), TIEG, and TIEG2. The genomic targets of these regulators will be identified in synchronized human cells using the genome-wide location analysis technique, which combines conventional chromatin immunoprecipitation (ChIP) with DNA microarray technology. The information regarding the genomic targets of the cell cycle regulators, along with gene expression levels of the target genes, will be used to construct a model for the regulation of the human cell cycle. In addition to the scope of this proposal, insight gained from this work will reveal how the cell cycle regulators regulate global gene expression and diverse stage-specific functions to produce a continuous cycle of cellular events. It should also facilitate mapping other regulatory networks in human.
| Boyer, Laurie A; Lee, Tong Ihn; Cole, Megan F et al. (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947-56 |
