Graduate Program
Biological Sciences
Degree Name
Master of Science (MS)
Semester of Degree Completion
2009
Thesis Director
Gary Bulla
Thesis Committee Member
Steven Daniel
Thesis Committee Member
Zhiwei Liu
Abstract
When hepatomas (liver cancer cells) are fused with fibroblasts (undifferentiated body cells), there is complete extinguishing of all tissue-specific gene expression. Once it was discovered that many hybrid cell lines do not express needed transcription factors for liver-specific gene transcription, the factors were reintroduced and forced to express through the use of plasmids. Even if the two primary transcription factors were present in the system, downstream tissue-specific gene expression was not rescued. To examine potential mechanisms for the repression of liver-specific gene expression in hepatoma x fibroblast hybrid cells, chromatin immunoprecipitation (ChlP) was used. This procedure allows the liver-specific gene promoters to be analyzed for the binding of transcription factors in vivo.
When analyzed, it was found that some hepatoma x fibroblast hybrids, previously assigned the cell line designations FR2 and FTRl 6, actually produced the liver-specific transcription factor Hepatocyte Nuclear Factor I-alpha (HNFla.) which bind the promoter of some liver-specific genes but not others. On the contrary, the transcription factor HNF 4a. was never found to bind the promoter of liver-specific genes in hybrid cell lines. This data suggests that an intricate and variable repression system may dictate HNFla. binding while HNF4a binding may be controlled through a less complex, more uniform mechanism. Overall, the data supported the theory that the cessation of liverspecific gene expression in hepatoma x fibroblast hybrids is controlled at the level of transcription, although the discovery of liver-specific transcription factors present in the FR hybrid cell line challenges the notion that this is a universal and total effect.
Recommended Citation
Angle, Jordan C., "Analysis Of Transcription Factor Promoter Binding In Rat Hepatoma/Fibroblast Hybrids" (2009). Masters Theses. 52.
https://thekeep.eiu.edu/theses/52