Wednesday, February 7, 2018

Introduction to Eukaryotic Gene Regulation

The Lac operon, a classic example of bacterial gene regulation, and set the stage for understanding Eukaryotic gene regulation.  While Eukaryotes can possess the equivalent of operators, there are more complex levels of regulation to help determine the differentiation and physiology of cells.  As we move to eukaryotic cells, we find that there are other ways that gene expression can be regulated.  Below are a few examples.  If you want to learn more about Eukaryotic Gene regulation, this page from the NCBI Bookshelf gives a good overview: Regulation of Transcription in Eukaryotes.
  • Transcriptional control:  This is control of the promoter and operator, and is very similar to what was seen with the Lac operon.
  • Enhancers and Activators: Enhancers are sequences on the DNA that are found away from the initiation site (promoter).  Activators are proteins that bind to enhancer sequences and help regulate the RNA Polymerase complex.  This allows for variable expression of the gene.  Eliminating one enhancer does not abolish transcription, but can reduce the efficiency of transcirption.
  • Epigenome:  This occurs in both prokaryotes and eukaryotes.  In eukaryotes, the epigenome is noted by chemical changes to DNA and histone molecules that result in changes to the chromatin strand.  These changes can "lock down" genes, preventing even the recognition of the promoter.
    • IMPORTANT:  the epigenome does not represent mutations.  Instead, it is a reversible chemical alteration to chromatin structure.
    • This chromatin alteration can be passed vertically to offspring.
    • Changes to the epigenome occur due to chemical signals and environmental changes (they change the organisms adaptation range).
  • DNA Methylation (Epigenetic):  Methylation of cytosine (the nitrogenous base of the nucleotide) prior to a promoter reduces transcription rates of the gene, or can inactivate the gene.
  • Post-Transcription regulation:  If you don't add the 5' cap, then RNA can't leave the nucleus.  If you don't add the 3' poly-A tail, RNA is digested.  If you don't splice out the introns, you don't have a code.  Prevention of post-transcriptional modification can play a role in gene expression.
Suggested Reading:
Eukaryotic Gene Regulation
Tissue Specific Gene Regulation
Gene Regulation in Eukaryotes (advanced)
Eukaryotic Gene Expression Problem Set (advanced)



Epigenome Videos

GOAL
At present, I want you to concentrate on gene regulation at the promoter.  This includes the concepts discussed in regards to the Lac and Trp operons, as well as enhancers and activators.  Having an idea of how chromatin remodeling works will also help in regards to eukaryotic gene regulation.  In subsequent semesters, these concepts will be the foundation for further exploration of gene expression.

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