Chapter 18: Regulation of Gene Expression
Terms in this set (82)
In response to chemical signals, prokaryotes can do what?
can turn off translation of their mRNA
What would occur if the repressor of an inducible operon were mutated so it could not bind to the operator?
Continuous transcription of the operon's genes
A lack of this nonprotein molecule would result in the inability of the cell to 'turn off' genes:
corepressor (nonprotein molecule)
The lactose operon is likely to be transcribed when
the cyclic amp and lactose levels are both high in the cell.
____________ use the product of a biosynthetic pathway to regulate gene expression
Inducible operons (biosynthetic= making something)
Using the metabolic needs of e. coli, explain why all genes aren't on all of the time:
e. coli living in the stomach of a human have to adapt to whatever the person eats, and they also need tryptophan for their own fuel. E. coli activate their own metabolic pathway to make trp in absence, but if the person eats it the presence inhibits enzyme 1 by feedback inhibition.
What are the two main ways of controlling metabolism in bacterial cells?
Regulation of Enzyme activity: feedback inhibition
Regulation of enzyme production: repress expression of the genes that code for the enzymes in this pathway.
In e. coli regulating trp synthesis, is it positive or negative inhibition?
negative because the rate decreases as concentration of product increases.
What is a promoter?
a site where RNA pol can bind to DNA to begin transcription
what is the operator?
a sequence of DNA that controls access of RNA pol to a cluster of functionally related genes. Positioned within promoter or between promoter & genes
List the 3 components of an operon and explain the role of each one:
promoter: where RNA pol binds to begin transcription. Operator: on/off sequence in or after promoter
Operon Genes: functionally related genes controlled by the same operator
when a single on/off switch can control a group of genes with the same function (transcription unit)
How does a repressor protein work?
can turn on/off an operon. binds to operator & blocks attachment of RNA pol to promoter
What are regulatory genes?
Genes that code for repressors or inducers for the operon that they control. Expressed continuously but at fluxuating levels
Explain inducible operons and describe one example
transcription is sually off but can be induced when a small molecule binds to regulatory protein. Inducer inactivates the repressor. Ex: the lac operon
Explain repressible operons and describe one example
transcription is usually on but can be inhibited when small molecule binds to regulatory protein. Repressor molecule activates the repressor protein. Ex: the trp operon
small molecule that cooperates with repressor protein to switch operon off
Compare and contrast the lac operon and the trp operon:
Lac operon: catabolic, inducible. Operon codes for enzymes to metabolize lactose, so it's inactive without lactose. Inducer inactivates repressor so genes can be transcribed. Trp Operon: Anabolic, repressible. Operon codes for enzymes to make trp, so its active without trp: repressible. repressor molecule activates repressor protein so genes can function.
What happens when a repressor is bound to the operator?
It switches off the operons if in active form (negative control)
What is CAP? how does CAP work?
catabolite activator protein is a regulatory protein that binds to DNA & stimulates transcription of a gene. Positive regulator.
Explain why CAP binding and stimulation of gene expression is positive regulation:
because CAP binds directly to the promoter so it directly stimulates gene expression
Describe the relationship between the glucose supply, cAMP, and CAP.
cAMP accumulates when glucose is scarce. When cAMP binds to CAP, CAP becomes active and binds to an upstream area of the lac promoter. This increases the affinity of RNA pol for the promoter. CAP facilitates RNA pol binding and increased rate of transcription. If glucose is in high concentration and cAMP is low, CAP detaches from the operon. Then RNA pol binds less efficiently and rate of transcription is decreased.
How can both repressible and inducible operons be negative regulators?
both need inducer/repressor proteins to bind to the regulatory protein in order to function.
Explain how the lac operon is under dual control:
stimulated by CAP, blocked by lac repressor. CAP controls rate, lac repressor controls if translation occurs at all.
What percentage of the genes of a typical human cell are expressed at any give time?
How much of human genes actually code for protein?
What is the common control point of gene expression for all organisms?
at transcription: regulation at this stage is often in response to signals coming from outside the cell (ex:hormones). For this reason, gene expression is often equated with transcription.
What occurs in histone acetylation? How does it affect gene expression?
Acetylation of histone tails promotes loose chromatin structure (beads on a string), permitting transcription. Acetyl groups are attached to lysines in histone tails, so their positive charges are neutralized and histone tails no longer bind to neighboring molecules.
What is DNA methylation? How does it affect gene expression?
When methyl groups are added to certain bases, that section of DNA becomes inactive. Removal of the methyl can allow transcription to occur: there are proteins that bind to methylated DNA & recruit enzymes to demethylate them.
The inactive mammalian X chromosome is heavily methylated. What is the result of this methylation?
it becomes inactive, and will stay this way not because it can't go back, but because the cell monitors is to stay untranscribable. This way different alleles of the same genes won't be expressed at the same time.
What is genomic imprinting, and how is it maintained?
Where methylation permanently regulates expression of either the maternal or paternal allele of particular genes at the start of development. (X chromosome methylation)
Explain epigenetic inheritance and give an example:
Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence. (modifications to chromatin that can be reversed.) ex: one identical twin getting schizophrenia, a genetically based disease, while the other twin is fine.
Histone code hypothesis:
specific combinations of modifications, rather than the overall level of histone acetylation, help determine the chromatin configuration, influencing transcription.
To initiate transcription, RNA pol II needs assistance of _______________.
Trancription factor proteins.
Explain how enhancers and activators interact with transcription factors to affect gene expression:
1. Activator proteins bind to distal control elements grouped as an enhancer in the DNA, upstream of the gene. 2. A DNA bending protein brings the bound activators closer to the promoter. GTF, mediator proteins, and RNA pol are nearby. 3. The activators bind to certain mediator proteins and GTF's, helping them form an active transcription initiation complex on the promoter.
Where can distal control elements be?
can be in an intron, can be grouped as enhancers or separate, and can be near or far from the promoter.
In prokaryotes, functionally related genes are usually clustered in a single operon. What has been found to be the case in eukaryotes?
each gene in a cluster of functionally related genes has its own promoter and is individually transcribed. Can be on the same chromosome or on different chromosomes.
A given gene may have _________ enhancers that are associated with ________________.
multiple enhancers that are associated with that gene and no other.
How can alternative RNA splicing result in different proteins derived from the same initial RNA transcript?
Different mRNA are produced from the same primary transcript, depending on what is treated as exons and what is treated as introns.
How can functionally related genes with different promoters and at different places in the chromosome be affected all at the same time?
Change in chromatin structure to make a whole group available or unavailable
Repressor specific transcription factors (STF) work in two ways:
1. turning off transcription even when activators are bound, by binding between the general transcription factors (GTF's) and the enhancer. 2. Not allowing binding of activators, by blocking that site.
General transcription factors (GTF) are _____ for all protein coding sequences. what do they do?
essential. They bind to other proteins and only when the whole transcription initiation complex is complete will RNA pol II begin.
Post-transcriptional control includes regulation of mRNA degradation. Explain how this affects translation:
mRNA are degraded in cytoplasm a few minutes after synthesis in bacteria (hours/days/weeks in euk), allowing patterns of protein synthesis to change quickly in response to stimuli.
How can proteins be activated and example:
Global control (of translation of all mRNAs) involves activation or inactivation of Transcription initiation factors. After fertilization, transcription of mRNA in eggs is triggered by activation of transcription initiation factors.
How can proteins be processed and example:
ex: cleavage of protein insulin = active insulin. Chemical modifications for functionality. Proteins for cell surface have sugars added to them
How can proteins be degraded and example (with nucleases):
enzymatic shortening of Poly-A tail & removal of 5' cap = nucleases chew up the mRNA. ex: cyclins that regulate the cell cycle need to be short lived for the cell to function properly. Marked by ubiquitin for destruction, this is recognized by proteasomes that degrade them.
Explain how proteins are degraded with proteasomes:
proteins are marked for destruction by ubiquitin molecules (requires ATP). Proteasome protein complexes then see this tag, unfold the protein, and put it in their central cavity. Enzymatic components of the proteasome then cut the protein into small peptides which can be further degraded by other enzymes in the cytosol.
What is the role played by noncoding RNAs?
To regulate gene expression. Regulation by noncoding RNAs occurs at mRNA translation & chromatin configuration.
What are the three processes that lead to the transformation of a zygote into an organism?
cell division, cell differentiation, and morphogenesis.
Explain what occurs in cell differentiation:
cells become specialized in structure and function, and these are organized into tissues and organs. Activities of a cell depend on the genes it expresses and the proteins it produces. Specific activators turn on the collection of genes whose products are needed in the cell. Materials placed into the cell by the mother set up a sequential program of gene regulation that's carried out as cells divide.
Explain what occurs in morphogenesis:
Th physical processes that give an organism its shape. Literally meaning, "creation of form." Changes in shape, motility, and other characteristics of the cells that make up sections of the embryo.
One of the noncoding RNAs that regulate gene expression is microRNA. Explain two modes of action of microRNAs (miRNAs):
1. Enzyme cuts each hairpin from the primary RNA transcript. 2. Second enzyme, the Dicer, trims the loop at the single stranded ends of the hairpin. 3. One strand of the double stranded RNA is degraded. The other strand then forms a complex with one or more proteins. 4. The miRnA can bind to any target mRNA that contains at least 6 bases of complementary sequence. 5. If miRna & mRNA bases are complementary all along their lenth, mRnA is degraded. If match is less complete, translation is blocked.
How are miRNAs formed?
formed from RNA precursors that fold back on themselves, forming short hairpin structures held together by Hbonds.
What happens when double-stranded RNA molecules are injected into a cell?
expression of a gene with the same sequence as the injected RNA is turned off. This is called RNA interference (RNAi) due to siRNAs.
How are siRNAs formed?
from much longer double stranded RNAs, which give rise to many siRNAs.
In addition to affecting mRNAs, siRNAs can cause......
remodeling of the chromatin structure. siRNAs form heterochromatin at centromeres. They bind to a certain protein complex and bring it to the centromere, where they recruit enzymes to make that area highly condensed heterchromatin.
How do different sets of activators come to be present in two cells? just name the two ways:
distribution of cytoplasmic determinants, and different inductive signals.
Explain the distribution of cytoplasmic determinants for how different sets of activators come to be present in two cells:
maternal substances in the egg that influence early development. They're unevenly distributed in the cytoplasm of the egg, so different cells end up with different amounts of molecules as the cells divide.
Explain the different inductive signals for how different sets of activators come to be present in two cells:
Signals to the embryonic cell from other embryonic cells in the vicinity. ex: binding of growth factors secreted by neighbouring cells. These signals cause changes in the target cell (induction) and send the cell down a noticeably differentiated path.
What is meant by determination? Explain what this means within an embryonic cell:
the events that lead to the observable differentiation of the cell. Not reversible, even if the determined cell is placed elsewhere in the embryo. Cells have become noticeably different in structure and function. Cells express the genes they'll need in the tissue they're destined for (tissue specific proteins, ex: liver makes albumin).
What are master regulatory genes, example, and what do they do?
master regulatory genes make proteins that will commit the cell to their destiny. ex: myoD protein stimulates expression of itself so the cell will stay this way.
Mutant bicoid (anterior) gene in drosophila mother=
embryo with posterior structures at both ends and no front half.
product of the Bicoid gene=
morphogen that determines the anterior end of a fly.
What are morphogens?
substances that establish an embryo's axes and features.
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?
Positional information controls pattern formation, development of front, back, top, bottom, and sides of embryo. Positional info is provided by cytoplasmic determinants and inductive signals. Tells the cell its relation to other cells & the body axes. Determines how the cell & its progeny will respond to future molecular signals.
What is controlled by homeotic genes?
pattern formation in late embryo, larva, and adult. Regulatory genes that cause placement of structures.
What are oncogenes?
cancer-causing genes that arise from a genetic change, leading to increase of proto-oncogene's protein product or in the activity of these molecules.
What are proto-oncogenes:
normal versions of oncogenes. They encode for proteins that stimulate normal cell growth & division.
What are three mechanisms for converting a proto-oncogene to an oncogene?
movement of DNA within the genome, amplification of a proto-oncogene, and point mutations in a control element of the proto-oncogene itself. All result from broken and incorrectly rejoined chromosomes.
movement of the DNA in the genome is a problem and will cause a proto-oncogene to become an oncogene because...
1. It could have a new promoter that caused excess production. 2. It could be transcribed over and over to make multiple copies.
What are egg polarity genes?
This is a different name for maternal effect genes, since they also set up the axes of an embryo.
Maternal effect genes=
when mutant in mother, mutant phenotype in offspring even if offspring genotype is normal. mRNA protein products of maternal effect genes are put in egg when it's still in the ovary.
Tumor suppressor genes code for...
proteins that prevent uncontrolled cell growth. Some TS proteins (TSP) repair damaged DNA, or control adhesions of cells to each other or to the ecm, or are components of cell signaling pathways that inhibit the cell cycle. Any mutation that decreases the amount of TSP increases the chance of cancer.
Steps of the cell stimulating pathway:
1. growth factor binds to receptor in plasma membrane. 2. Signal is related to a G protein called Ras that needs GTP bound to it to relay signal. Hyperactive Ras protein (product of oncogene) issues signals on its own. 3. The last kinase that the signal is relayed to activates a transcription activator that turns on one or more genes for proteins that stimulate the cell cycle.
What does the p53 tumor suppressor gene do?
activated p53 promotes transcription of the gene for a protein that inhibits the cell cycle, ensuring that damaged DNA cells aren't replicated. Or, it just blocks the cells cycle until the damage can be repaired. When DNA damage is irreparable, p53 activates genes whose products cause apoptosis.
Why does the chance of cancer increase greatly with age?
Mutations accumulate throughout life, and more than one somatic mutation is needed to produce all the changes of a full-on cancer cell.
6 Simple steps of colorectal cancer development:
1. loss of tumor suppressor gene in normal colon epitherial cells 2. small benign growth (polyp) occurs 3. Activation of ras oncogene 3. loss of DCC tumor suppressor gene 4. Larger benign growth occurs (adenoma) 5. loss of TSG p53 5. more mutations 6. malignant tumor forms (carcineroma)
How do cancer-causing viruses work?
may donate an oncogene to the cell, disrupt a tumor-suppressor gene, or convert a proto-oncogene to an oncogene. Some viruses also produce proteins that inactivate p53 and other tumor-suppressor proteins, making the cell more prone to cancer.
If a particular operon encodes enzymes for making an essential amino acid and is regulated like the trp operon, then
the amino acid acts as a corepressor.
What would occur if the repressor of an inducible operon were mutated so that it couldn't bind to the operon?
continuous transcription of the operon's genes
The functioning of enhancers is an example of
transcriptional control of gene expression
Within a cell, the amount of protein made using a given mRNA molecule depends partly on
the number of introns present in the mRNA.