29. Regulation of gene expression

Last updated on November 19, 2018 at 17:16

Summary

  • A gene contains promoters, and the part that is transcribed. The promoter is a part of DNA that RNA polymerase can bind to.
  • RNA polymerase’s affinity to the promoters regulate how often RNA polymerase binds to the gene, and therefore how often the gene is transcribed.
  • An operon is a cluster of genes that are under regulation by the same promoter.
  • The lac operon in bacteria contains genes for the enzymes that are needed for lactose metabolism. When lactose is unavailable, the lac repressor stops transcription of the lac operon, to prevent waste of resources.
  • The SOS response in E. coli is the cellular response to great DNA damage. When DNA damage is detected, RecA protein breaks down LexA repressor, which usually represses genes that try to fix the DNA as a last resort.
  • Gene regulation in trans is mediated by small RNAs that either expose or block the ribosome-binding site on mRNA, to increase or decrease translation, respectively
  • Gene regulation in cis is mediated when specific ligands bind certain RNA structures called aptamers. When this binding occurs, the mRNA coils, so the ribosome-binding site is blocked, and the ribosome cannot bind to the mRNA to translate it.
  • Histone modification can vary gene expression in many ways. Acetylation of histones activates genes while methylation inactivates.
  • Nucleosomes can be remodelled by complexes like SWI/SNF, which regulates gene expression
  • DNA is methylated, which affects the transcription. DNA methylation is inherited from parent so a small degree.

Gene regulation

The buildup of a normal gene.

The DNA of a cell contains 4 different types of genes. Housekeeping genes are genes that should always be expressed, like transcription machinery, proteins needed for energy conversion and so on. Cell-type specific genes are turned on in specific cell-types, and give a cell it’s unique properties. Developmental regulatory genes are specific to certain stages during growth and development of a person. Inducible genes are not normally expressed, but induced in response to external stimuli, like hormones or heat shock.

Recall that RNA polymerase can switch out its σ-subunit depending on what needs to be expressed. The σ70 subunit binds to the promoters of housekeeping genes. σ32 binds to heat-shock genes.

An operon is a cluster of genes that are controlled by the same promoters, and which are transcribed together. The best-known example of operons is the lac operon in E. coli. This operon codes for genes that are needed for lactose metabolism. However, to save resources, this operon should not be expressed when there is no lactose available for the bacteria anyway. The lac repressor represses these genes when lactose is not available. When lactose is available, the lac repressor stops repressing these genes, so genes needed for lactose metabolism are expressed. However, when both glucose and lactose are available, lactose metabolism should be inhibited anyway, because glucose metabolism is more efficient than lactose metabolism.

Several 3d-structures in proteins can bind to DNA. Among these are helix-turn-helix, zinc fingers, homeodomain, leucine zippers, and helix-loop-helix. The Lac repressor is an example of a protein with helix-turn-helix, while helix-loop-helix is found in HIF-1α, which you will read more about later.

The SOS response in bacteria is a cellular response to great DNA damage. It works by a combination of LexA repressor and RecA protein. E. coli contains genes for many proteins that try to fix this DNA damage. However, during normal conditions, these genes are inhibited by LexA repressor. When DNA damage occurs, RecA protein binds to the damage. RecA then breaks down LexA, so that it doesn’t repress the SOS response genes anymore. When this repression is broken, the genes are expressed, so the proteins can try to fix the DNA damage.

Bacterial mRNA can be regulated in two ways, in trans or in cis. Every mRNA contains a site where the ribosome binds to it. If this site is difficult to reach, then the mRNA has more trouble binding to the ribosome, so it’s translated less often. If the site is easy to reach, it’s translated more often. In trans regulation uses small RNA molecules that bind to mRNA to either block or expose the ribosome-binding site. mRNAs can contain structures called aptamers. These aptamers can bind certain ligands, like TPP, glycine or adoMet. When the aptamers bind these ligands, the mRNA coils, which makes the ribosome-binding site harder to reach. This is called in cis regulation.

Gene expression in eukaryotes is different than in prokaryotes on several levels. In bacteria, transcription and translation happens at the same time and place (in the cytosol), while in eukaryotes, they’re separated in both time and space. This means that they don’t take place simultaneously, and not in the same cellular compartment. In bacteria, most genes are active while only certain ones are repressed, while in eukaryotes, most genes are inactive, and only the ones that are needed are activated.

Bacteria contain no histones, and have different chromatin structure than eukaryotes. In eukaryotes, epigenetics is important, but they are non-existent in bacteria. Epigenetics is the study in how changes in DNA that don’t change the DNA sequence can be inherited. DNA methylation and histone modification are the main mechanisms of epigenetics. DNA methylation mostly decreases gene expression, and is inherited from parents.

Histone modification radically modifies gene expression

Recall that a nucleosome is the complex of DNA around a histone. Many different types histones exist, and by change the histone type, the gene availability of that nucleosome changes.

Histones can be covalently modified to change the gene expression. Acetylation of a histone relaxes the DNA structure around it, which activates the genes around the histone, while methylation inactivates them. Acetylation and deacetylation is catalysed by histone acetyltransferase.

All lysine residues on histones can be methylated. Histone H3 contains nineteen lysine residues. This creates billions of possible methylation patters, each with a different impact on gene regulation. This is called the histone code.

Certain protein complexes, like SWI/SNF, can remodel the nucleosomes, to influence gene expression.

A few of the factors that influence gene expression.

 


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30. Mitochondrial protein synthesis, mitochondrial genome

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