Wednesday, April 1, 2009
Regulatory DNA
On page 206, Sean Carroll discusses the various parts of genes. “In addition to the coding part of a gene, every gene also contains noncoding DNA sequences that are regulatory,” (Carroll 206). Discuss how these regulatory sections of DNA work – where they are located, how they are formed, how are they turned on and off, etc. In the book, Carroll talks about these regulatory genes in relation to the pelvic spines in stickleback fish. What other examples of organisms can you find in which regulatory genes play a role?
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These sections of DNA, called operons, work in response to either positive or negative feedback by either stimulating or inhibiting the production of a certain molecule. Operons consist of the regulatory gene and the promoter region, which includes the operator. The operator is the "switch" which either activates or inactivates a certain task or activity. In bacteria, as discussed in the textbook, the lac operon is naturally repressed by the lac repressor. However, when lactose enters the body, an isomer of the lactose called allolactose, the inducer, binds to the lac repressor, removing its ability to attach to the operator, which allows the lactose to be properly digested and converted into enzymes.
ReplyDeleteThe benefit of having operons control various processes is that they allow for the maximum possible efficiency in a body. If there is no lactose available to be digested, then why waste time, and more importantly energy, in trying to? That is one purpose of having an operon to control the digestion of lactose. In terms of the stickleback fish discussed by Carroll on page 206, the presence of an operon allows for the fish to adapt more easily to its environment, as the absence of long armor allows it to escape the grasp of predators which feast on young fish with long pieces of armor that slow it down.
Regulatory genes are switch like devices that determine where and when each gene is used and not used on the entire DNA sequence. More specifically a regulatory gene would be referred to as the spawning mother of the repressor. The regulatory gene is located some distance before the operon and has its own promoter and controls the promoter for the DNA sequence in preparation to be read. The regulatory gene is constantly being read and transcribed but a slower rate.
ReplyDeleteThe operon is everything including the promoter, the operator, and the genetic sequence ready to be read by the RNA polymerase which will soon transcribe it into mRNA to be translated later into proteins and enzymes that will affect the phonotypical characteristics of the organism. The promoter region of the operon usually has a TATA box where the beginning nucleotide sequence is TATATA so the RNA polymerase knows where to start and usually the end of the nucleotide sequence ends with TGA for instance.
The repressor, made from the regulatory gene, can either be turning on or turning off the operator allowing the RNA polymerase to come and transcribe the specific DNA sequence. The repressor works with a co repressor that activates the repressor to either induce the operon into working or restrict the operon into working by attaching to the operator either blocking the RNA polymerase from reading the sequence or not.
There are also other regulatory functions such as Cyclic amp receptor proteins which when activated attaches to the allosteric site of the CRP which in turns binds to the region before the promoter which in turns bends the DNA which somehow allows RNA polymerase to bind more easily and read the DNA more readily. So if the cyclic amp receptor proteins were missing from an organism’s environment for a long enough time then eventually it could cause a fossilization of a specific DNA sequence because it’s never read enough and eventually becomes to mutate and change. It’s never read enough because the CRP then doesn’t bend the DNA which helps it to be read.
Other organisms that have exhibited regulatory genes are every animal on the face of the earth. They all have regulatory genes that play a role in its everyday life style. Take for instance the moths which have various genes regulated by regulatory genes. The owl monkeys that have adapted nonfunctional opsein gene because they are nocturnal and part of their nucleotide sequence in their operon had a point mutation with an early TGA to end the transcription rendering the rest of the important information about color distinction useless.
Regulatory genes are switch like devices that determine where and when each gene is used and not used on the entire DNA sequence. More specifically a regulatory gene would be referred to as the spawning mother of the repressor. The regulatory gene is located some distance before the operon and has its own promoter and controls the promoter for the DNA sequence in preparation to be read. The regulatory gene is constantly being read and transcribed but a slower rate.
ReplyDeleteThe operon is everything including the promoter, the operator, and the genetic sequence ready to be read by the RNA polymerase which will soon transcribe it into mRNA to be translated later into proteins and enzymes that will affect the phonotypical characteristics of the organism. The promoter region of the operon usually has a TATA box where the beginning nucleotide sequence is TATATA so the RNA polymerase knows where to start and usually the end of the nucleotide sequence ends with TGA for instance.
The repressor, made from the regulatory gene, can either be turning on or turning off the operator allowing the RNA polymerase to come and transcribe the specific DNA sequence. The repressor works with a co repressor that activates the repressor to either induce the operon into working or restrict the operon into working by attaching to the operator either blocking the RNA polymerase from reading the sequence or not.
There are also other regulatory functions such as Cyclic amp receptor proteins which when activated attaches to the allosteric site of the CRP which in turns binds to the region before the promoter which in turns bends the DNA which somehow allows RNA polymerase to bind more easily and read the DNA more readily. So if the cyclic amp receptor proteins were missing from an organism’s environment for a long enough time then eventually it could cause a fossilization of a specific DNA sequence because it’s never read enough and eventually becomes to mutate and change.
It’s never read enough because the CRP then doesn’t bend the DNA which helps it to be read.
Other organisms that have exhibited regulatory genes are every animal on the face of the earth. They all have regulatory genes that play a role in its everyday life style. Take for instance the moths which have various genes regulated by regulatory genes. The owl monkeys that have adapted nonfunctional opsein gene because they are nocturnal and part of their nucleotide sequence in their operon had a point mutation with an early TGA to end the transcription rendering the rest of the important information about color distinction useless.
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ReplyDeleteYes it is true that operons are a method of gene regulation, but these are found only in prokaryotic cells (and in very rare cases some eukaryotic organisms). Eukaryotic organisms use different methods to regulate certain genes. In organisms like the stickleback fish mentioned on page 206, operons are definitely not used to regulate gene expression, but rather they most likely use methods such as DNA methylation/demethylation.
ReplyDeleteThere are many stages of gene expression where the expression can be regulated such as transcription, RNA processing, translation, or post-translation, but the most common method is methylation as mentioned above. In the case of the stickleback fish, only a section of the Pitx-1 gene is being regulated because the gene is a “toolkit” gene, and complete changes might be catastrophic for the stickleback fish. Therefore, the pelvic fin region regulation region of the Pitx-1 gene is where methylation might be occurring. If methylation is indeed the mechanism for regulating the gene, then in the fish with a full pelvis, the region that is noncoding but stimulates pelvic fin development would be highly methylated, meaning that many methyl groups are attached to the base pairs, which makes any enzymes unable to bind to the DNA at this site. Therefore, even if the region of DNA is not for coding, enzymes will still most likely have to bind at these regulation sites in order to initiate a sequence of events to stimulate the coding portion of the gene to be expressed. In the pelvic reduced species, the opposite most likely occurs, and there is a low level of methylation and access to these regulator portions of the DNA is open.
There are other possible mechanisms that the stickleback uses to regulate expression of the Pitx-1 gene such as histone acetylation, where acetyl groups are attached to the histone proteins loosening the coiled DNA making it easier for enzymes to bind. Also there are regions analogous to enhancers on the DNA called silencers, upstream of the coding portions of DNA that could be responsible for the “silencing” of the pelvic fin portion of the gene. The reason I strongly believe methylation is mainly responsible (because it is most likely a combination), is that DNA methylation is usually the mechanism for long-lasting regulation of genes. Since these conditions are permanent for the fish as the expression of their genes has been altered through natural selection, pelvic fin development is regulated starting at the cellular differentiation stage of the embryo, good evidence that DNA methylation is the cause.
There are several primary measures by which DNA regulates itself. The first is DNA methlyation. There are specific sequences of nucleotides that –CH3 groups can bind to. This binding provides a physical barrier to RNA polymerase during transcription. Some times this method of regulation can be used to permanently shut off either maternal or paternal alleles at the start of development, a process refereed to as genomic imprinting. Also there are specific sequences that
ReplyDelete–COOCH3 can bind to. This serves to loosen the DNA from the histone it is wrapped around, therefore allowing RNA polymerase to transcribe a nearby gene. This process is called Histone Acetylation.
Another method of DNA regulation comes through transcription factors. Transcription factors are proteins that bind to noncoding segments of DNA upstream of a gene. The DNA regions to which a transcription factor binds is called a enhancer region. An activator protein then binds to this region, which aids in the binding of the transcription factors. When the transcription factor binds to the enhancer and activator, the DNA is stimulated to fold in such a manner that the transcription factors bind to the promoter region of the gene. This then stimulates RNA polymerase to transcribe the gene. This can be used as a regulatory pathway by cells due to the fact that cells can control what transcription factors are in the nucleus at what time. For example all steroid and some protein hormones function by entering the nucleus and acting as a transcription factor, thus activating a gene. Due to the fact that a gene cannot be transcribed without its transcription factors, this provides an effective means of regulation.
Finally, operons are regulated by noncoding DNA sequences. In operons, sequences of DNA in the promoter region can bind to repressor proteins (made by upstream regulatory genes), which blocks RNA transcriptase, thus preventing transcription. The repressor protein can be activated or deactivated based of concentrations of certain substances in the cell. In repressible operons, such as the trp operon, the repressor protein is activated by the end product of the gene. In inducible operons, such as the lac operon, the repressor protein is inactivated by an inducer (a substance that the end product of the operon acts on).
Regulatory mechanisms are employed by all cells, one example being the hox gene. Hox genes function in differentiating tissues during development, and are shut down after gastrulation by removing the necessary transcription factors.
http://en.wikipedia.org/wiki/Regulation_of_gene_expression#Examples_of_gene_regulation
http://dev.biologists.org/cgi/content/full/132/13/2931