10.1:
Cell Specific Gene Expression
Every cell in the body of a multicellular organism possesses the same DNA; however, different cell types have notable structural and functional differences which can be attributed to the differential expression of genes in the cell.
Additionally, specific cells express different genes over time due to changes in the cell or organism. The variety of RNA and proteins produced enables cells to carry out their unique functions at the appropriate times.
Liver cells, called hepatocytes, express a different set of genes compared to neurons.
For example, liver cells produce alcohol dehydrogenase, an enzyme that breaks down toxic alcohols into acetaldehyde, which then can further be metabolized to produce carbon dioxide and water.
In contrast, neurons produce neurexins, a group of proteins in the brain that helps transmit information from one neuron to an adjacent one.
Cells have mechanisms to control gene expression at multiple regulatory steps before, during, and after transcription and translation. However, transcriptional regulators are common because it prevents the synthesis of mRNA transcripts.
During liver development in humans, the transcription factors C/EBP α, C/EBP β, and Hepatocyte Nuclear Factor-1 contribute to the liver-specific expression of alcohol dehydrogenase genes.
Gene expression is also regulated in response to the extracellular environment.
When blood glucose levels decrease, the pancreas secretes the hormone glucagon. When exposed to glucagon, liver cells express phosphoenolpyruvate carboxykinase, a protein required for the production of glucose from non-carbohydrate precursors.
10.1:
Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with the stages of development. Prior to differentiation into liver cells, the cells express genes involved in the cell cycle, DNA replication, and proliferation. Later in development, genes involved in epithelial differentiation and blood coagulation are highly expressed. Once cells differentiate into hepatocytes, the expression of genes involved in liver-specific functions increases, such as those involved in lipid metabolism and cholesterol regulation.
Gene expression can be regulated at many points including transcription, translation, RNA processing and transport, and post-translational modifications. Common methods of regulating expression are factors that bind directly to DNA to regulate the transcription of a particular gene. Gene expression in the liver can be regulated by the transcription factors C/EBPα, C/EBPβ, and Hepatocyte Nuclear Factor-1, among others. Regulation can occur prior to transcription by altering the histones contained in chromatin. These modifications result in either loosening or tightening of the DNA structure, thereby respectively preventing or allowing transcriptional regulators to access the DNA. Different cell types have different covalent modifications and histone variants, which results in the variation in gene accessibility.
Cells are subject to environmental changes and express different genes in response to these extracellular stimuli. Glucose is an important source of energy, and as its concentration in the bloodstream fluctuates, an organism must respond with appropriate changes in gene and protein expression. When blood glucose levels decrease, the pancreas secretes the hormone glucagon. This hormone signals the liver to initiate the production of phosphoenolpyruvate carboxykinase (PEPCK), a protein required to produce glucose from non-carbohydrate precursors. Glucagon induces the transcription of this gene by indirectly stimulating transcription factors C/EBPα and C/EBPβ to bind to the PEPCK promoter. When blood glucose levels are high, the pancreas secretes the hormone insulin; the PEPCK gene has an insulin-responsive sequence that inhibits its transcription.
Suggested Reading
- Alberts et al., 6th edition; pages 369-374.
- Lodish et al., 8th edition; pages 363- 364
- Park, Edwards A. Austin L. Gurney, Steven E. Nizielski, Parvin Hakimi, Zhodan Caot, Antoon MoormanY, and Richard W. Hanson. “Relative Roles of CCAAT/Enhancer-binding Protein β and cAMP Regulatory Element-binding Protein in Controlling Transcription of the Gene for Phosphoenolpyruvate Carboxykinase (GTP)” Journal of Biological Chemistry 268, No. 1, (1993): 613-619