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Tissue-specific expression of hepatic functions. Genetic aspects.
Annals of the New York Academy of Sciences
|January 1, 1986
Summary
Cell fusion hybrids often lose tissue-specific gene expression, a process called extinction. Researchers identified specific fibroblast chromosomes that regulate liver gene expression in these hybrids, defining new genetic loci.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Intertypic cell hybrids frequently exhibit extinction, the loss of tissue-specific gene products from parent cells.
- Understanding the genetic regulation of this phenomenon is crucial for cell biology and developmental studies.
Purpose of the Study:
- To investigate the genetic basis and complexity of extinction in hepatoma x fibroblast hybrids.
- To identify specific genetic loci responsible for the negative regulation of liver-specific gene expression.
Main Methods:
- Utilized 15 liver-specific cDNA clones as probes to measure mRNA expression in hybrid cells.
- Analyzed gene expression in a series of hepatoma x fibroblast hybrids with varying fibroblast chromosome content.
- Examined hybrid segregants that had lost specific fibroblast chromosomes.
Main Results:
- Thirteen out of 15 liver-specific mRNAs showed extinction in complete hepatoma x fibroblast hybrids.
- Reexpression of these mRNAs was observed in hybrid segregants lacking specific fibroblast chromosomes.
- Extinction of specific hepatic markers was linked to the presence of individual fibroblast chromosomes.
Conclusions:
- Defined and localized discrete genetic loci, termed Tse loci, that govern liver-specific gene expression.
- These Tse loci act in trans to negatively regulate the expression of hepatic genes in hybrid cells.
- Provides insights into the epigenetic control mechanisms underlying cell differentiation and gene silencing.