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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK076284-03
Application #
7533489
Study Section
Special Emphasis Panel (ZRG1-F08-G (20))
Program Officer
Podskalny, Judith M,
Project Start
2007-01-01
Project End
2009-08-31
Budget Start
2009-01-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2009
Total Cost
$36,240
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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