gene silencing

Examples of gene silencing in the following topics:

• Epigenetic Alterations in Cancer

  • Common in cancer cells, silencing genes, which occur through epigenetic mechanisms, include modifications to histone proteins and DNA.
  • Silencing genes through epigenetic mechanisms is very common in cancer cells and include modifications to histone proteins and DNA that are associated with silenced genes.
  • When these modifications occur, the gene present in that chromosomal region is silenced.
  • In cancer cells, silencing genes through epigenetic mechanisms is a common occurrence.
  • Mechanisms can include modifications to histone proteins and DNA associated with these silencing genes.

• Altered Gene Expression in Cancer

  • Cancer, a disease of altered gene expression, is the result of gene mutations or dramatic changes in gene regulation.
  • Cancer can be described as a disease of altered gene expression.
  • There are many proteins that are turned on or off (gene activation or gene silencing) that dramatically alter the overall activity of the cell.
  • This can be the result of gene mutation or changes in gene regulation (epigenetic, transcription, post-transcription, translation, or post-translation).
  • Therefore, changes in histone acetylation (epigenetic modification that leads to gene silencing), activation of transcription factors by phosphorylation, increased RNA stability, increased translational control, and protein modification can all be detected at some point in various cancer cells.

• Aquifex, Thermocrinis, and Related Bacteria

  • The presence of the insertion in the Thermotogae species may be due to a horizontal gene transfer.
  • In the 16S rRNA gene trees, the Aquificae species branch in the proximity of the phylum Thermotogae (another phylum comprising hyperthermophilic organisms) close to the archaeal-bacterial branch point.
  • However, a close relationship of the Aquificae to Thermotogae, and the deep branching of Aquificae, is not supported by phylogenetic studies based upon other gene/protein sequences and also by conserved signature indels in several highly-conserved universal proteins.
  • Comparison of the A. aeolicus genome to other organisms showed that around 16% of its genes originated from the Archaea domain.
  • A. aeolicus is also known as one of the few bacterial species capable of doing gene silencing.

• The trp Operon: A Repressor Operon

  • E. coli can also synthesize tryptophan using enzymes that are encoded by five genes.
  • These five genes are next to each other in what is called the tryptophan (trp) operon .
  • Because the repressor protein actively binds to the operator to keep the genes turned off, the trp operon is negatively regulated and the proteins that bind to the operator to silence trp expression are negative regulators.
  • This physically blocks the RNA polymerase from transcribing the tryptophan genes.
  • When tryptophan is absent, the repressor protein does not bind to the operator and the genes are transcribed.

• Epigenetic Control: Regulating Access to Genes within the Chromosome

  • The human genome encodes over 20,000 genes; each of the 23 pairs of human chromosomes encodes thousands of genes.
  • This type of gene regulation is called epigenetic regulation.
  • If a gene is to be transcribed, the histone proteins and DNA are modified surrounding the chromosomal region encoding that gene.
  • If a gene is to remain turned off, or silenced, the histone proteins and DNA have different modifications that signal a closed chromosomal configuration.
  • Modifications affect nucleosome spacing and gene expression.

• Epistasis

  • The B gene controls black (B_) vs. brown (bb) color, while the E gene controls yellow (ee) color.
  • Genes may also oppose each other with one gene modifying the expression of another.
  • The alleles that are being masked or silenced are said to be hypostatic to the epistatic alleles that are doing the masking.
  • In this case, the C gene is epistatic to the A gene.
  • Thus, the C gene is epistatic to the A gene.

• RNA Splicing

  • Gene expression is the process that transfers genetic information from a gene made of DNA to a functional gene product made of RNA or protein.
  • In eukaryotes, the gene contains extra sequences that do not code for protein.
  • Alternative splicing allows more than one protein to be produced from a gene and is an important regulatory step in determining which functional proteins are produced from gene expression.
  • Alternative splicing is a process that occurs during gene expression and allows for the production of multiple proteins (protein isoforms) from a single gene coding.
  • Equally as important are the silencers and enhancers that are found on the messenger RNAs, also known as cis-acting sites.

• X-Inactivation

  • The presence of extra X chromosomes in a cell is compensated for by X-inactivation in which all but one X chromosome are silenced.
  • Females possess two X chromosomes, while males have only one; therefore, if both X chromosomes remained active in the female, they would produce twice as much product from the genes on the X chromosomes as males.
  • However, even inactivated X chromosomes continue to express a few genes, and X chromosomes must reactivate for the proper maturation of female ovaries.

• Gene Families

  • Gene families are groups of functionally related genes arising from a duplicated gene.
  • A gene family is a set of several similar genes, formed by duplication of a single original gene, that generally have similar biochemical functions .
  • If the genes of a gene family encode proteins, the term protein family is often used in an analogous manner to gene family.
  • In contrast, gene complexes are simply tightly linked groups of genes, often created via gene duplication (sometimes called segmental duplication if the duplicates remain side-by-side).
  • Unequal crossing over generates gene families.

• Tracking Cells with Light

  • In molecular biology, researchers use a reporter gene that they attach to a regulatory gene of interest.
  • Reporter genes ideally have distinguishable properties that can be easily detected and measured.
  • To introduce a reporter gene into an organism, scientists place the reporter gene and the gene of interest in the same DNA construct to be inserted into the cell or organism.
  • It is important to use a reporter gene that is not natively expressed in the cell or organism under study, since the expression of the reporter is being used as a marker for successful uptake of the gene of interest.
  • Reporter gene used as an indication of the regulatory sequence expression in the cell.