Ch 18 Regulation of Gene Expression

What are the two main ways of controlling metabolism in bacterial cells?

1. Cells can adjust the activity of enzymes already present. This is a fairly fast response, which relies on the sensitivity of many enzymes to chemical cues that increase or decrease their catalytic activity. 2. Cells can adjust the production level of certain enzymes; that is, they can regulate the expression of the genes encoding the enzymes.

List the three components of an operon, and explain the role of each one.

1. Operator: the segment of DNA that operates as the "switch" 2. Promoter: the site where RNA polymerase can bind with DNA to begin transcription 3. Genes: nucleotide sequences that specifically encode subunits of the enzyme

What three processes lead to the transformation of a zygote into the organism?

1. cell division 2. cell differentiation 3. morphogenesis

What percentage of the genes of a typical human cell is expressed at any given time?

20%

Explain the multistep model of cancer development by using the specific example of colorectal cancer.

Affecting the colon and/or rectum, this type of cancer is one of the best understood. Changes in a tumor parallel a series of genetic changes, including mutations affecting several tumor-suppressor genes (such as p53) the ras proto-oncogene. Mutations of tumor-suppressor genes often entail loss (deletion) of the gene. Other mutation sequences can also lead to colorectal cancer. See page 376 of text for the labeled figure.

The inactive mammalian X chromosome is heavily methylated. What is the result of this methylation?

After an X chromosome is inactivated in a particular cell, all mitotic descendants of that cell have the same inactive X. Thus, if a female is heterozygous for a sex-linked trait, about half her cells will express one allele, while the others will express the alternative allele.

distribution of cytoplasmic determinants

After fertilization, early mitotic divisions distribute the zygote's cytoplasm into separate cells. The nuclei of these cells may thus be exposed to different cytoplasmic determinants, depending on which portions of the zygotic cytoplasm a cell received. The combination of cytoplasmic determinants in a cell helps determine its developmental fate by regulating expression of the cell's genes during the course of cell differentiation.

What are three mechanisms for converting a proto-oncogene to an oncogene?

An oncogene arises from a genetic change that leads to an increase either in the amount of the proto-oncogene's protein product or in the intrinsic activity of each protein molecule. The genetic changes that convert proto-oncogenes to oncogenes are movement of DNA within the genome, amplification of a proto-oncogene, and point mutations in a control element or in the proto-oncogene itself.

How can both repressible and inducible operons be negative regulators?

Both repressible and inducible operons can be negative regulators as long as the operons are switched off by the active form of the repressor protein. In the case of the lac operon, allolactose induces enzyme synthesis not by acting directly on the genome, but by freeing the lac operon from the negative effect of the repressor. Remember that gene regulation is said to be positive only when a regulatory protein interacts directly with the genome to switch transcription on

Why is CAP binding and stimulation of gene expression positive regulation?

By facilitating the binding of RNA polymerase to the promoter and thereby increasing the rate of transcription, the attachment of CAP to the promoter directly stimulates gene expression, qualifying CAP as positive regulation.

In prokaryotes, functionally related genes are usually clustered in a single operon. What has been found to be the case in eukaryotes?

Co-expressed eukaryotic genes, such as genes coding for the enzymes of a metabolic pathway, are typically scattered over different chromosomes. In these cases, coordinate gene expression depends on the association of a specific combination of control elements with every gene of a dispersed group.

Operons have not been found in eukaryotic cells, and the genes coding for the enzymes of a particular metabolic pathway are often scattered over different chromosomes. What is a plausible mechanism for the coordination of gene expression?

Coordinate control of dispersed genes in a eukaryotic cell often occurs in response to chemical signals from outside the cell. A steroid hormone, for example, enters a cell and binds to a specific intracellular receptor protein, forming a hormone-receptor complex that serves as a transcription activator.

How can alternative RNA splicing result in different proteins derived from the same initial RNA transcript?

Different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns. Regulatory proteins specific to cell type control intron-exon choices by binding to regulatory sequences within the primary transcript.

One of the noncoding RNAs that regulate gene expression is microRNA. Explain the two modes of action of microRNAs.

If mRNA and mRNA bases are complementary all along their length, the mRNA is degraded (left side of figure); if the match is less complete, translation is blocked (right side of figure). See page 365 of text for the labeled figure.

Describe the relationship between glucose supply, cAMP, and CAP

If the amount of glucose in the cell increases, the cAMP concentration falls, and with cAMP, CAP detaches from the operon. B/c CAP is inactive, RNA polymerase binds less efficiently to the promoter, and transcription proceeds at a low level

Compare and contrast the lac operon and the trp operon.

In both, the entire transcription unit is under the command of one main operator and promoter. The lac is an inducible operon, while the trp is repressible. In both, regulation involves negative control of genes, b/c operons are switched off by the active form of the repressor protein

What occurs in histone acetylation? How does it affect gene expression?

It is the attachment of acetyl groups to certain amino acids of histone proteins. Such binding promotes the folding of chromatin into a more compact structure; when this bind occurs, chromatin has a looser structure. As a result, transcribing proteins have easier access to genes in an acetylated region

What is DNA methylation? What role may it play in gene expression?

It is the process of adding methyl groups to DNA bases. At least in some species, DNA methylation seems to be essential for the long-term inactivation of genes that occurs during normal cell differentiation in the embryo

What mechanism is involved in the beginning of tumor growth?

Mutations in the genes that normally regulate cell growth and division in somatic cells can lead to cancer. An oncogene is a gene found in viral or cellular genomes that is involved in triggering molecular events that can lead to cancer. A proto-oncogene is a normal cellular gene that has the potential to become an oncogene.

What process ensures that all the tissues and organs of an organism are in their characteristic places? Where do the molecular cues that control this process arise?

Pattern formation. The molecular cues that control pattern formation, collectively called positional info, are provided by cytoplasmic determinants and inductive signals

Use the sketch below to explain how enhancers and activators interact with transcription factors to affect gene expression.

See page 360 of text for the labeled figure.

Posttranscriptional control includes regulation of mRNA degradation. Explain how this affects translation.

The longer mRNA is in the cytoplasm,the more protein that can be formed by translation. In general, prokaryotes degrade their mRNA more quickly than eukaryotes

different inductive signals

The molecules conveying these signals within the target cell are cell-surface receptors and other proteins expressed by the embryo's own genes. In general, the signaling molecules send a cell down a specific developmental path by causing changes in its gene expression that eventually result in observable cellular changes.

How can proteins be activated, processed, and degraded? Give an example or describe each process.

The process of making proteins through activation can best be seen in the developing embryo. Many mRNA molecules are made ahead of fertilization, but they do not have a poly-A tail and are therefore not active. At the appropriate time, an enzyme in the cytoplasm adds the adenines, activating the mRNA and producing proteins. A second method of activation is the zygote wide release of translation initiation factors that triggers a burst of protein synthesis. Proteins are often processed by altering amino acids or changing the sequence of amino acids to form an active, functioning protein. Finally, the length of time each protein functions in the cell is strictly regulated by means of selective degradation utilizing proteasomes.

Explain how proteins are targeted for degradation, and give a specific example of when this might occur.

To mark a particular protein for destruction, the cell commonly attaches molecules of a small protein ubiquitin to the protein. Proteasomes then recognize ubiquitin-tagged proteins and degrade them. The importance of proteasomes is underscored by the findings that mutations making specific cell cycle proteins impervious to proteasome degradation can lead to cancer.

What are regulatory genes?

a gene that codes for a protein, such as a repressor, that controls the transcription of another gene or group of genes

What is a promoter?

a specific nucleotide sequence in the DNA of a gene that binds RNA polymerase, positioning it to start transcribing RNA at the appropriate place

What is an operon?

a unit of genetic function found in bacteria and phages, consisting of a promoter, and operator, and a coordinately regulated cluster of genes whose products function in a common pathway

How does a repressor protein work?

binds to the operator and blocks attachment of RNA polymerase to the promoter, preventing transcription. A repressor protein is specific for the operator of a particular operon

What is controlled by homeotic genes?

control placement and spatial organization of body parts in animals, plants, and fungi by controlling the developmental fate of groups of cells

Gene expression can be regulated by modifications of the chromatin. Distinguish between heterochromatin and euchromatin as to their structure and activity.

heterochromatin: eukaryotic chromatin that remains highly compacted during interphase and is generally not transcribed euchromatin: the less condensed form of eukaryotic chromatin that is available for transcription

What is the operator, and what does it do?

in bacterial and phage DNA, is a sequence of nucleotides near the start of an operon to which an active repressor can attach. The binding of the repressor prevents RNA polymerase from attaching to the promoter and transcribing the genes of the operon

Explain what is meant by epigenetic inheritance.

inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence of a genome

What happens when a repressor is bound to the operator?

it blocks attachments of RNA polymerase to the promoter, preventing transcription of the genes

Tumor-suppressor genes help prevent uncontrolled cell growth. One that is found mutated (and therefore nonfunctional) in more than 50% of human cancer is p53. So important is the p53 gene that it is sometimes called the "guardian angel of the genome." Describe the double whammy that results from mutation of p53.

p53 acts in several ways to prevent a cell from passing on mutations due to DNA damage. If mutations do accumulate and the cell survives through many divisions—as is more likely if the p53 tumor-suppressor gene is defective or missing—cancer may ensue.

Fig 18.4

pg 354

What is CAP and how does it work?

refers to Catabolite Activator Protein, and is a regulatory protein that binds to DNA and stimulates transcription of a gene

It is now known that much of the RNA that is transcribed is not translated into protein. These RNAs are called noncoding RNAs. What is role played by these RNAs?

regulating gene expression

Distinguish inducible and repressible operons.

repressible: usually on, but can be inhibited (repressed) when a specific small molecule binds allosterically to a regulatory protein. An example is the trp operon inducible: usually off but can be stimulated (induced) when a specific small molecules interacts with a regulatory protein. An example is the lac operon

Even though all cells of an organism have the same genes, there is differential gene expression. What does this mean?

the expression of different sets of genes by cells with the same genome

What is genomic imprinting, and how is it maintained?

the phenomenon in which expression of an allele in offspring depends on whether the allele is inherited from the male or female parent

morphogensis

the physical process that gives an organism its shape

cell differentiation

the process by which cells become specialized in structure and function

What is determination, and what does it mean within an embryonic cell?

the progressive restriction of developmental potential in which the possible fate of each cell becomes more limited as an embryo develops. At the end of determination, a cell is committed to its fate.

What is the common control point of gene expression for all organisms?

transcription