Identifying the conserved transcriptional regulatory network of hepatocytes will provide insight into the mechanisms of tissue specification and human diseases such as diabetes. To this aim, the genomic regions occupied by key regulators in murine hepatocytes will be experimentally determined using chromatin immunoprecipitation combined with microarrays. A new joint binding deconvolution algorithm will identify the precise location of binding events in both the newly acquired mouse data and previously obtained human hepatocyte data. Using the binding events identified in both species, a likelihood model of the conserved regulatory network between human and mouse will be constructed. Finally, by examining closely related mammalian sequence data, the evolutionary history of the hepatocyte regulatory network can be inferred to provide insight into how gene regulation is maintained during the course of evolution. ? ? ?
|Dowell, Robin D; Ryan, Owen; Jansen, An et al. (2010) Genotype to phenotype: a complex problem. Science 328:469|
|Bumgarner, Stacie L; Dowell, Robin D; Grisafi, Paula et al. (2009) Toggle involving cis-interfering noncoding RNAs controls variegated gene expression in yeast. Proc Natl Acad Sci U S A 106:18321-6|
|Gerber, Georg K; Dowell, Robin D; Jaakkola, Tommi S et al. (2007) Automated discovery of functional generality of human gene expression programs. PLoS Comput Biol 3:e148|
|Odom, Duncan T; Dowell, Robin D; Jacobsen, Elizabeth S et al. (2007) Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 39:730-2|