In eukaryotes, the DNA molecules or associated histones can be chemically modified in such a way as to influence transcription; this is called
epigenetic regulation . Methylation of certain cytosine nucleotides in DNA in response to environmental factors has been shown to influence use of such DNA for transcription, with
DNA methylation commonly correlating to lowered levels of gene expression. Additionally, in response to environmental factors,
histone proteins for packaging DNA can also be chemically modified in multiple ways, including
acetylation and deacetylation, influencing the packaging state of DNA and thus affecting the availability of loosely wound DNA for transcription. These chemical modifications can sometimes be maintained through multiple rounds of cell division, making at least some of these epigenetic changes heritable.
This
video describes how epigenetic regulation controls gene expression.
What stops or allows transcription to proceed when attenuation is operating?
What determines the state of a riboswitch?
Describe the function of an enhancer.
Describe two mechanisms of epigenetic regulation in eukaryotes.
Resolution
Although Mark survived his bout with necrotizing fasciitis, he would now have to undergo a skin-grafting surgery, followed by long-term physical therapy. Based on the amount of muscle mass he lost, it is unlikely that his leg will return to full strength, but his physical therapist is optimistic that he will regain some use of his leg.
Laboratory testing revealed the causative agent of Mark’s infection was a strain of group A streptococcus (Group A strep). As required by law, Mark’s case was reported to the state health department and ultimately to the Centers for Disease Control and Prevention (CDC). At the CDC, the strain of group A strep isolated from Mark was analyzed more thoroughly for methicillin resistance.
Methicillin resistance is genetically encoded and is becoming more common in group A strep through horizontal gene transfer. In necrotizing fasciitis, blood flow to the infected area is typically limited because of the action of various genetically encoded bacterial toxins. This is why there is typically little to no bleeding as a result of the incision test. Unfortunately, these bacterial toxins limit the effectiveness of intravenous antibiotics in clearing infection from the skin and underlying tissue, meaning that antibiotic resistance alone does not explain the ineffectiveness of Mark’s treatment. Nevertheless, intravenous antibiotic therapy was warranted to help minimize the possible outcome of sepsis, which is a common outcome of necrotizing fasciitis. Through genomic analysis by the CDC of the strain isolated from Mark, several of the important virulence genes were shown to be encoded on prophages, indicating that transduction is important in the horizontal gene transfer of these genes from one bacterial cell to another.
Gene expression in prokaryotes is largely regulated at the point of transcription. Gene expression in eukaryotes is additionally regulated post-transcriptionally.
Prokaryotic structural genes of related function are often organized into
operons , all controlled by transcription from a single promoter. The regulatory region of an operon includes the promoter itself and the region surrounding the promoter to which transcription factors can bind to influence transcription.
Although some operons are
constitutively expressed , most are subject to regulation through the use of
transcription factors (repressors and activators). A
repressor binds to an
operator , a DNA sequence within the regulatory region between the RNA polymerase binding site in the promoter and first structural gene, thereby physically blocking transcription of these operons. An
activator binds within the regulatory region of an operon, helping RNA polymerase bind to the promoter, thereby enhancing the transcription of this operon. An
inducer influences transcription through interacting with a repressor or activator.
The
trp operon is a classic example of a
repressible operon . When tryptophan accumulates, tryptophan binds to a repressor, which then binds to the operator, preventing further transcription.
The
lac operon is a classic example an
inducible operon . When lactose is present in the cell, it is converted to allolactose. Allolactose acts as an inducer, binding to the repressor and preventing the repressor from binding to the operator. This allows transcription of the structural genes.
The
lac operon is also subject to activation. When glucose levels are depleted, some cellular ATP is converted into cAMP, which binds to the
catabolite activator protein (CAP) . The cAMP-CAP complex activates transcription of the
lac operon. When glucose levels are high, its presence prevents transcription of the
lac operon and other operons by
catabolite repression .
Small intracellular molecules called
alarmones are made in response to various environmental stresses, allowing bacteria to control the transcription of a group of operons, called a regulon.
Bacteria have the ability to change which
σ factor of RNA polymerase they use in response to environmental conditions to quickly and globally change which regulons are transcribed.
Prokaryotes have regulatory mechanisms, including
attenuation and the use of
riboswitches , to simultaneously control the completion of transcription and translation from that transcript. These mechanisms work through the formation of stem loops in the 5’ end of an mRNA molecule currently being synthesized.
There are additional points of regulation of gene expression in prokaryotes and eukaryotes. In eukaryotes,
epigenetic regulation by chemical modification of DNA or histones, and regulation of RNA processing are two methods.
Fill in the blank
The DNA sequence, to which repressors may bind, that lies between the promoter and the first structural gene is called the ________.
What are two ways that bacteria can influence the transcription of multiple different operons simultaneously in response to a particular environmental condition?