MCB Chapter 19 genetic and epigenetic regulation

chromatin

- A complex of DNA, RNA, and proteins that gives chromosomes their structure; chromatin fibers are either 30 nm in diameter or, in a relaxed state, 10 nm.

major places where gene regulation in eukar can take place

- the first level of control is at the chromosome, even before transcription takes place. - The manner in which DNA is packaged in the nucleus in eukaryotes provides an important opportunity for regulating gene expression. Regulation at this level of gene expression is determined in part by whether the proteins necessary for transcription can gain physical access to the genes they transcribe. - at the level of an entire chromosomes

allosteric effect****

- when the activator protein combines with a small molecule in the cell and undergoes a change in shape that alters its binding affinity for DNA -In some cases, the activator cannot bind with DNA on its own, but combining with the small molecule changes its shape and its ability to bind with particular sequences in the DNA. The presence of the small molecule in the cell therefore results in transcription of the gene. -Genes subject to this type of POSITIVE CONTROL typically encode proteins needed only when the small molecule is present in the cell. For example, in E. coli, the genes for the breakdown of the sugar arabinose are normally repressed in the absence of the sugar because a regulatory protein binds the DNA in such a way as to prevent transcription. In the presence of arabinose, however, the shape of the protein is altered so that it binds a different site in the DNA, allowing transcription of the genes. For other genes, activator proteins can bind DNA only when a small molecule is absent from the cell. These genes typically encode proteins needed for synthesis of the small molecule. In E. coli, the genes for synthesis of the amino acid cysteine are regulated in this fashion. -negative regulation. In this case, the DNA in its native state can recruit the RNA polymerase complex, and transcription takes place at a constant rate unless something turns it off. What turns it off is binding with a protein called a repressorAgain, the binding site for the repressor can be upstream of the promoter, downstream of the promoter, or overlapping with the promoter. -As with positive control, the ability of the repressor to bind DNA is often determined by an allosteric interaction with a small molecule. A small molecule that interacts with the repressor and prevents it from binding DNA is called an inducer ADDED: - induces a conform. change - it can cause a protein to have an increased ability or a decrease ability (causing it to fall off) - this gives a better sense of control for having gene expression on or off

much of the regulation that occurs after transcription (regulation of mRNA stability, regulation of translation, posttranslational modifications) is determined by the physiological state of your cells, which in turn is strongly influenced by your lifestyle choices

-For example, your cells can synthesize 12 of the amino acids in proteins, but if any of these is present in sufficient amounts in your diet, it is absorbed during digestion and not synthesized. The amino acid you ingest blocks the synthetic pathway through feedback effects. -This cascade of regulatory effects in both directions can occur because the expression of any gene is regulated at multiple levels, and because there is much feedback and signaling back and forth between nucleus and cytoplasm. It is because of these feedback and signaling mechanisms that the effects of lifestyle choices can be propagated up the regulatory hierarchy. For example, it has been shown that dietary intake of fats and cholesterol affects not only the activity of enzymes directly involved in the metabolism of fats and cholesterol, but also the levels of transcription of the genes encoding these enzymes by affecting the activity of their regulatory transcription factors. Similarly, lifestyles that combine balanced diets with exercise and stress relief have been shown to increase transcription of genes whose products prevent cellular dysfunction and decrease transcription of genes whose products promote disease.

imprinting

-In humans and other mammals, about 100 genes are repressed by chemical modification such as DNA methylation in the germ line in a sex-specific manner. -For some genes, the allele of the gene inherited from the mother is imprinted and therefore silenced, so only the allele inherited from the father is expressed. For other imprinted genes, the allele of the gene inherited from the father is imprinted and therefore silenced, so only the allele inherited from the mother is expressed. The imprinting persists in somatic cells through the lifetime of the individual but is reset in its germ line according to the individual's sex.

dosage compensation

-The differential regulation of X-chromosomal genes in females and in males.

transcriptional regulation

-The mechanisms that collectively regulate whether or not transcription occurs. -Transcriptional regulation in eukaryotic cells requires the coordinated action of many proteins that interact with one another and with DNA sequences near the gene. INVOLVES: -general transcription factors A set of proteins that bind to the promoter of a gene whose combined action is necessary for transcription. The transcription factors are brought there by one of the proteins that bind to a short sequence in the promoter called the TATA box, which is usually situated 25-30 nucleotides upstream of the nucleotide site where transcription begins. - Once bound to the promoter, the transcription factors recruit the components of the RNA polymerase complex, the enzyme complex that synthesizes the RNA transcript complementary to the template strand of DNA. Where in the many steps of transcription initiation does regulation occur? --The first point at which transcription can be regulated is in the recruitment of the general transcription factors and components of the RNA polymerase complex. Recruitment of these elements is controlled by proteins called regulatory transcription factors - Transcription does not occur if the regulatory transcription factors do not recruit the components of the transcription complex to the gene. Some regulatory transcription factors recruit chromatin remodeling proteins that allow physical access to a gene. Other regulatory transcription factor have two binding sites, one of which binds with a particular DNA sequence in or near a gene known as an enhancer -Hundreds of different regulatory transcription factors control the transcription of thousands of genes. Some bind with enhancers and stimulate transcription; others bind with DNA sequences known as silencers and repress transcription. -Enhancers and silencers are often in or near the genes they regulate, but in some cases they may be many thousands of nucleotides distant from the genes. A typical gene may be regulated by multiple enhancers and silencers of different types, each with one or more regulatory transcription factors that can bind with it. Transcription takes place only when the proper combination of regulatory transcription factors is present in the same cell -combinatorial control Regulation of gene transcription by means of multiple transcription factors acting together.

x inactivation how X-inactivation works

-The process in mammals in which dosage compensation occurs through the inactivation of one X chromosome in each cell in females. -Soon after a fertilized egg with two X chromosomes implants in the mother's uterine wall, one X chromosome at random is inactivated. The inactive state persists through cell division, so in each cell lineage, the same X chromosome that was originally inactivated remains inactive. The result is that a normal female is a mosaic, or patchwork, of tissue. In some patches, the genes in the maternal X chromosome are expressed (and the paternal X chromosome is inactivated), whereas in other patches, the genes in the paternal X chromosome are expressed (and the maternal X chromosome is inactivated). The term "inactive X chromosome" is a slight exaggeration since a substantial number of genes are still transcribed, although usually at a low level. -In calico cats, the orange and black fur colors are due to different alleles of a single gene in the X chromosome. In a heterozygous female, X-inactivation predicts discrete patches of orange and black, and this is exactly what is observed. (The white patches on a calico cat are due to an autosomal gene.) HOW IT WORKS: - A key player is a small region in the X chromosome called the X-chromosome inactivation center (XIC), which contains a gene called Xist (X-inactivation specific transcript). The Xist gene is normally transcribed at a very low level, and the RNA is unstable, but in an X chromosome about to become inactive, Xist transcription markedly increases. The transcript undergoes RNA splicing, but it does not encode a protein. Xist RNA is therefore an example of a noncoding RNA. -Instead of being translated, the processed Xist RNA coats the XIC region, and as it accumulates, the coating spreads outward from the XIC until the entire chromosome is coated with Xist RNA. The presence of Xist RNA along the chromosome recruits factors that promote DNA methylation, histone modification, and other changes associated with transcriptional repression. -The Xist gene is both necessary and sufficient for X-inactivation: If it is deleted, X-inactivation does not occur; if it is inserted into another chromosome, it inactivates that chromosome.

RNA editing

-The process in which some RNA molecules become a substrate for enzymes that modify particular bases in the RNA, thereby changing its sequence and sometimes what it codes for.

chromatin remodeling Chemical modifications

-The process in which the nucleosomes are repositioned to expose different stretches of DNA to the nuclear environment. CHEMICAL MODIFICATION -One way in which chromatin is remodeled is by chemical modification of the histones around which DNA is wound - Modification usually occurs on histone tails, strings of amino acids that protrude from the histone proteins in the nucleosome. Individual amino acids in the tails can be modified by the addition (or later removal) of different chemical groups, including methyl groups (—CH3) and acetyl groups (—COCH3). - Most often, methylation or acetylation occurs on the lysine residues of the histone tails. Some of these modifications tend to activate transcription and others to repress transcription. The pattern of modifications of the histone tails constitutes a histone code that affects chromatin structure and gene transcription. Modification of histones takes place at key times in development to ensure that the proper genes are turned on or off, as well as in response to environmental cues. -In many eukaryotic organisms, gene expression is also affected by chemical modification of certain bases in the DNA, the most common of which is the addition of a methyl group to the base cytosine -DNA methylation recruits proteins that affect changes in chromatin structure, histone modification, and nucleosome positioning that restrict access of transcription factors to gene promoters. Methylation of cytosines often occurs in cytosine bases that are adjacent to guanosine bases on a DNA strand. Cytosine methylation often occurs in CpG islands, which are clusters of adjacent CG nucleotides located in or near the promoter of a gene. Heavy cytosine methylation is associated with transcriptional repression of the gene near the CpG island. The methylation state of a CpG island can change over time or in response to environmental signals, providing a way to turn genes on or off. Cells sometimes heavily methylate CpG islands of transposable elements or viral DNA sequences that are integrated into the genome, thus preventing the expression of genes in the foreign DNA

epigenetic

-Together, the modification of cytosine bases, changes to histones, and alterations in chromatin structure - That is, epigenetic mechanisms of gene regulation typically involve changes not to the DNA sequence itself but to the manner in which the DNA is packaged. -Epigenetic modifications can in some cases affect gene expression. They can be inherited through mitotic cell divisions, just as genes are, but are often reversible and responsive to changes in the environment. Furthermore, epigenetic modifications present in sperm or eggs are sometimes transmitted from parent to offspring, meaning that these chemical modifications can be inherited.

almost all mRNA molecules have

-a 5′ cap, a 5′ untranslated region (5′ UTR), an open reading frame (ORF) containing the codons that determine the amino acid sequence of the protein, a 3′ untranslated region (3′ UTR), and a poly(A) tail - The 5′ UTR and 3′ UTR may contain regions that bind with proteins. These RNA-binding proteins help control mRNA translation and degradation. The UTRs may also contain binding sites for small regulatory RNAs. - During development,some RNA-binding proteins interact with molecular motors that transport the mRNA to particular regions of the cell. In other cases, the proteins are only in particular locations in the cell and repress translation of the mRNAs that are transported there and to which they bind. By either transport or repression, these proteins cause the mRNA to be translated only in certain places in the cell. -The cap structure is one of the main recognition signals for translation initiation, which requires the coordinated action of about 25 proteins. These proteins are present in most cells in limiting amounts, and so at any one time while some mRNAs from a gene are being translated, other mRNAs transcribed from the same gene may not have a translation initiation complex assembled. Upon formation, the initiation complex moves along the 5′ UTR, scanning for an AUG codon (the initiation codon) to allow the complete ribosome to assemble and begin translation. -The 3′ UTR and the poly(A) tail are also important in translation initiation. The efficiency of translation initiation is greatly increased by physical contact between a protein that binds the poly(A) tail and one that binds the 5′ cap. The physical contact creates a loop in the mRNA, bringing the 3′ end of the mRNA into proximity with the start site for translation. In fact, most mRNA sequences that regulate translation are present in the 3′ UTR.

RNA splicing provides an opportunity for regulating gene expression

-because the same primary transcript can be spliced in different ways to yield different proteins in a process called alternative splicing. This process takes place because what the spliceosome—the splicing machinery—recognizes as an exon in some primary transcripts, it recognizes as part of an intron in other primary transcripts. The alternative-splice forms may be produced in the same cells or in different types of cell. Alternative splicing accounts in part for the observation that we produce many more proteins than our total number of genes. By some estimates, over 90% of human genes undergo alternative splicing.

how proteins can alter the phenotype of the cell or organism (posttranslational modification)

-by affecting metabolism, signaling, gene expression, or cell structure. After translation, proteins are modified in multiple ways that regulate their structure and function. - Regulation at this level is essential because some proteins are downright dangerous. For example, proteases such as the digestive enzyme trypsin must be kept inactive until secreted out of the cell. If they were not, their activity would kill the cell. These types of protein are often controlled by being translated in inactive forms that are made active by modification after secretion. -Correct folding is important because improperly folded proteins may form aggregates that are destructive to cell function. Many diseases are associated with protein aggregates, including Alzheimer's disease, Huntington's disease, and the human counterpart of mad cow disease. -Posttranslational modification also helps regulate protein activity. Many proteins are modified by the addition of one or more sugar molecules to the side chains of some amino acids. This modification can alter the protein's folding and stability, or target the molecule to particular cellular compartments. Reversible addition of a phosphate group to the side groups of amino acids such as serine, threonine, or tyrosine is a key regulator of protein activity -Introduction of the negatively charged phosphate group alters the conformation of the protein, in some cases switching it from an inactive state to an active state and in other cases the reverse. Because the function of a protein molecule results from its shape and charge (Chapter 4), a change in protein conformation affects protein function.

Gene regulation in prokaryotes****

-is simpler than gene regulation in eukaryotes since DNA is not packaged into nucleosomes, mRNA is not processed, and transcription and translation are not separated by a nuclear envelope. - In prokaryotes, expression of a protein-coding gene entails transcription of the gene into messenger RNA and translation of the messenger RNA into protein. Each of these levels of gene expression is subject to regulation. ADDED: -Euka promoter: TATA box -Proka promoter: has two regions recognized by the RNA polym; those being: sequences located about 10 and 35 base pairs upstream of the transcription start site. These promoter sequences are called the -10 (aka pribnow box) and -35 sequences. - transcription factor is called sigma. RNA polm will only be able to transcribe the gene of interest if it binds to the promoter sequences (pribnow box and -35) + the sigma factors - REGULATION: Prok need a level of control in order to save energy. Since there are so many proteins involved in transcription. - Positive regulation: ---Term described about how an activator protein works. ---- an activator protein must bind at a specific site (upstream from the RNA poly) to recruit the RNA polymerase and allow for transcription to start. -----The main players are DNA, the RNA polymerase complex, and a regulatory protein called a transcriptional activator (TB) - Negative regulation ----prevents transcription from occurring (a repressor) ---a repressor protein must bind at a specific site preventing the RNA poly from transcribing the gene. ****the site where an activator or a repressor bind can vary; it can be before, after, or a part of the promoter.

two types of small regulatory RNA

-small interfering RNA (siRNA) A type of small double-stranded regulatory RNA that becomes part of a complex able to cleave and destroy single-stranded RNA with a complementary sequence. - microRNA (miRNA) Small, regulatory RNA molecules that can cleave or destabilize RNA or inhibit its translation. -Both types of small RNA are transcribed from DNA and form hairpin structures, or stem-and-loops, stabilized by base pairing in the stem. Enzymes in the cytoplasm specifically recognize these structures and cleave the stem from the hairpin, then further cut the stem into small, double-stranded fragments 20-25 base pairs in length. -One of the two strands from each RNA fragment is incorporated into a protein complex known as RISC (RNA-induced silencing complex). The small, single-stranded RNA targets the RISC to specific RNA molecules by base pairing with short regions in the target. Depending on the type of small regulatory RNA, the RNA sequence in the RISC, and the particular type of RISC, the small regulatory RNA may result in chromatin remodeling, degradation of RNA transcripts, or inhibition of mRNA translation

small regulatory RNA

-small size allows for easy synthesis in the lab - their sequences can be desinged to target transcripts - it is A short RNA molecule that can block transcription, cleave or destabilize RNAA, or inhibit mRNA translation.

The initial transcript, called the primary transcript, undergoes several types of modification, collectively called RNA processing

-that includes the 5′ end and a string of tens to hundreds of adenosine nucleotides to the 3′ end to form the poly(A) tail. These modifications are necessary for the RNA molecule to be transported to the cytoplasm and recognized by the translational machinery. The poly(A) tail also helps to determine how long the RNA will persist in the cytoplasm before being degraded. RNA processing is therefore an important point where gene regulation can occur -In eukaryotes, the primary transcript of many protein-coding genes is far longer than the messenger RNA ultimately used in protein synthesis. The long primary transcript consists of regions that are retained in the messenger RNA (the exons) interspersed with regions that are excised and degraded (the introns). The introns are excised during RNA splicing

bacteriophage Virus that infects bacterial cells.

-the best known example is bacteriophage λ (lambda), which infects cells of E. coli. -Upon infection, the linear DNA of the phage genome is injected into the bacterial cell, and almost immediately the ends of the molecule join to form a circle. In normal cells growing in nutrient medium, the usual outcome of infection is the lytic pathway, shown on the left in Fig. 19.20. In the lytic pathway, the virus hijacks the cellular machinery to replicate the viral genome and produce viral proteins. After about an hour, the infected cell undergoes lysis and bursts open to release a hundred or more progeny phage capable of infecting other bacterial cells. -The alternative to the lytic pathway is lysogeny, shown on the right in Fig. 19.20. In lysogeny, the bacteriophage DNA and the bacterial DNA undergo a process of recombination at a specific site in both molecules, which results in a bacterial DNA molecule that now includes the bacteriophage DNA. Lysogeny often takes place in cells growing in poor conditions. The relative sizes of the DNA molecules in Fig. 19.20 are not to scale. In reality, the length of the bacteriophage DNA is only about 1% of that of the bacterial DNA. When the bacteriophage DNA is integrated by lysogeny, the only bacteriophage gene transcribed and translated is one that represses the transcription of other phage genes, preventing entry into the lytic pathway. The bacteriophage DNA is replicated along with the bacterial DNA and transmitted to the bacterial progeny when the cell divides. Under stress, such as exposure to ultraviolet light, recombination is reversed, freeing the phage DNA and initiating the lytic pathway. -At the molecular level, the choice between the lytic and lysogenic pathways is determined by the positive and negative regulatory effects of a small number of bacteriophage proteins produced soon after infection. Which pathway results depends on the outcome of a competition between the production of a protein known as cro and that of another protein known as cI. If the production of cro predominates, the lytic pathway results; if cI predominates, the lysogenic pathway takes place. -Fig. 19.21 shows the small region of the bacteriophage DNA in which the key interactions take place. Almost immediately after infection and circularization of the bacteriophage DNA, transcription takes place from the promoters PL and PR. Transcription of genes controlled by the PR promoter results in a transcript encoding the proteins cro and cII. The cro protein represses transcription of a gene controlled by another promoter PM, which encodes the protein cI. In normal cells growing in nutrient medium, proteases present in the bacterial cell degrade cII and prevent its accumulation. With cro protein preventing cI expression and cII protein unable to accumulate, transcription of bacteriophage genes in the lytic pathway takes place, including those genes needed for bacteriophage DNA replication, those encoding proteins in the bacteriophage head and tail, and, finally, those needed for lysis. -Alternatively, in bacterial cells growing in poor conditions, reduced protease activity allows cII protein to accumulate. When cII protein reaches a high enough level, it stimulates transcription from the promoter PE. The transcript from PE includes the coding sequence for cI protein, and the cI protein has three functions: 1.It binds with the operator OR and prevents further expression of cro and cII. 2.It stimulates transcription of its own coding sequence from the promoter PM, establishing a positive feedback loop that keeps the level of cI protein high. 3.It binds with the operator OL and prevents further transcription from PL.

structural gene

A gene that codes for the sequence of amino acids in a polypeptide chain. EXAMPLE: Bacteria that contain mutations that eliminate function of the lacZ gene (denoted lacZ- mutants), or those that eliminate function of the lacY gene (denoted lacY- mutants), cannot utilize lactose as a source of energy. Without a functional product from lacY, lactose cannot enter the cell, and without a functional product from lacZ, lactose cannot be cleaved into its component sugars. A functional form of β-galactosidase (lacZ+) and of permease (lacY+) are both essential for the utilization of lactose and for cell growth. -Regulation of the lacZ and lacY structural genes is controlled by the product of another structural gene, called lacI, which encodes a repressor protein. Located between lacI and lacZ are a series of regulatory sequences for lacZ and lacY that include a promoter, lacP, whose function is to recruit the RNA polymerase complex and initiate transcription, and an operator, lacO, which is the binding site for the repressor

operon****

A group of functionally related genes located in tandem along the DNA and transcribed as a single unit from one promoter; the region of DNA consisting of the promoter, the operator, and the coding sequence for the structural genes. -The lactose operon is negatively regulated by the repressor protein encoded by the lacI gene. That is, the structural genes of the lactose operon are always expressed unless the operon is turned off by a regulatory molecule, in this case the repressor. Fig. 19.16 shows what the operon looks like in the absence of lactose. The lacI gene, encoding the repressor protein, is expressed constantly at a low level. The repressor protein binds with the operator (lacO), the RNA polymerase complex is not recruited, and transcription does not take place. -The configuration of the lactose operon in the presence of lactose is shown in Fig. 19.17. When lactose is present in the cell, the repressor protein is unable to bind to the operator, RNA polymerase is recruited, and transcription occurs. In other words, lactose acts as an inducer of the lactose operon since it prevents binding of the repressor protein. The inducer is not actually lactose itself, but rather an isomer of lactose called allolactose, which differs in the way the sugars are linked. Lactose in the cell is always accompanied by a small amount of allolactose, and so induction of the lactose operon occurs in the presence of lactose. -The binding of the inducer to the repressor results in an allosteric change in repressor structure that inhibits the protein's ability to bind to the operator. The absence of repressor from the operator allows the RNA polymerase complex to be recruited to the promoter, and the polycistronic mRNA is produced. The resulting lactose permease allows lactose to be transported into the cell on a large scale, and β-galactosidase cleaves the molecules to allow the constituents to be used as a source of energy and carbon. The lactose operon is therefore an example of negative regulation by a repressor, whose function is modulated by an inducer. ADDED: - Lac operon the role of the lac operon is to express the enzymes for transport and metabolism of lactose into glucose and galactose. - an operon is a region of DNA containing regulatory regions (e.g promoter and the gene it controls) - Lac Z ( a protein)codes for B-galactosidase ( an enzyme that breaks down lactose) - Lac Y codes for lactose permease ( an enzyme that allows lactose into the cell so it can be metabloized) - The two keys protein products ( lactose permease and B-galactosidase) of the lac operon that are needed to transport and metabloze lactose. These two proteins are made from one mRNA. Prok are unqiue in that way becase they have polycistronic mRNA ( mRNA that can code for multiple genes) Lac operon is a polycistronic mRNA. This also includes many ribosome binding sites in front of each coding region that allows for translation of of the protein products. - one promoter, multiple genes, multiple ribosome binding sites. ** ---Lacl coding sequence translates into a repressor protein ( prevents the expression of B-galactosidase and lactose permease when lactose isn't around) Has its own promoter becuase it is not part of the operon itself - CRP- cam binding site: ---- site where the protein CRP binds and is able to faciliate the binding of mRNA poly when lactose is present. - negative regulation of the lac operon in the absence of lactose: ---lacl promoter (the repressor) is always is on which means it is constantly being made, it is called consititive promoter. ---if there is no lactose around the repressor bind to the operator sequence that exits after the lacl promoter bu before the the lacz and lacy gene. This causes no translation which results in no gene products associated with lactose metablosim being made ---- the Lac operon is repressed when: there is no lactose present and the lac repressed is bound to the lac O site Removing the repressor in the presence of lactose: - when lactose is present, a small amount gets converted to alolactose it binds to the repressor and the repressor is then falls off the opertor, which allows transcription of the componets for lactose metabliosm. and allows RNA pol to bind to the promoter and transcription can occur. - alolactose causes an allosteric change and the repressor can no longer bind to the promter site. POSITIVE REGULATION of the lac operon by CRP-cAMP: - in low/no glucose, cyclic AMP (cAMP) is high. The cAMP receptor protein (CRP) binds cAMP. CRP-cAMP can now bind near the lac operon regulatory region, facilitating binding of RNA pol. lacz and y are transcribed. - cAMP binds to CRP and then the complex that is created binds to a special DNA sequcence upstream from the promoter region allowing transcription for lactose metabloism to occur. - low glucose=lac operon is on as long as the repressor is not bound to the operator WHEN GLUCOSE IS PRESENT: - in high glucose cAMP is low so CRP can't bind the DNA. RNA pol is not recruited to transcribe the lac Z and Y genes. - in high glucose the lac operon is off.

Predict the consequence of a mutation in the lacI repressor gene that produces repressor protein that is able to bind to the operator, but not able to bind allolactose.

A mutation in the repressor gene that does not allow the repressor protein to bind allactose means that the repressor will never be blocked from binding the lactose operon promoter. This will lead to a cell that is not able to produce β-galactosidase in the presence or absence of lactose. In other words, the lactose operon will not be inducible.

polycistronic mRNA

A single molecule of messenger RNA that is formed by the transcription of a group of functionally related genes located next to one another along bacterial DNA.

Explain how the ability of a large, multisubunit protein molecule to bind a specific DNA sequence can be altered when it binds with a small molecule no larger than a single amino acid.

Binding with the small molecule results in a conformational change in one part of the protein that initiates a chain of interactions that propagate and alter its structure at sites far removed from the small molecule. These changes may conceal amino acid side chains responsible for the original DNA-binding specificity and expose a new combination of amino acid side chains that have a different DNA-binding specificity.

constitutive

Describes expression of a gene that occurs continuously. -The most common constitutive phenotype resulted from a mutation in the lacI gene (lacI- mutants) that produced a defective repressor protein

gene expression

Different types of cell express different genes. The human body contains about 200 major cell types, and although for the most part they share the same genome, they look and function differently from one another because each type of cell expresses different sets of genes. For example, the insulin needed to regulate sugar levels in the blood is produced only by small patches of cells in the pancreas. Every cell in the body contains the genes that encode insulin, but only in these patches of pancreatic cells are they expressed

Which one of the following statements about gene regulation is incorrect? Gene regulation occurs at the level of the chromosome. Gene regulation occurs at the level of transcription. Gene regulation occurs at the translational level. Gene regulation occurs only in prokaryotes. Gene regulation occurs at the post-translational level.

Gene regulation occurs only in prokaryotes.

Which one of the following statements about mutations in the lactose operon is not correct? A lacI mutant would result in the loss of expression of repressor protein. In cells containing one mutant and one normal copy of lacI, the repressor is still expressed and lacZ and lacY will be expressed only in the presence of lactose. A lacI mutant would allow continuous or constitutive expression of both β-galactosidase and lactose permease. A mutation in the lacO sequence would allow continuous or constitutive expression of both β-galactosidase and lactose permease. In cells containing one mutant and one normal copy of lacO, lacZ and lacY are expressed only in the absence of lactose.

In cells containing one mutant and one normal copy of lacO, lacZ and lacY are expressed only in the absence of lactose.

Which one of the following statements most accurately describes methylation? Methyl groups are most often added to cytosines adjacent to guanine bases in or near the promoter sequence, decreasing the probability of gene expression. Methyl groups are most often added to cytosines adjacent to guanine bases in or near the promoter sequence, increasing the probability of gene expression. Methyl groups are most often added to adenine-thymine base pairs because they are held by only two hydrogen bonds, and this increases the probability of gene expression. Methyl groups are most often added to guanine-cytosine base pairs because they are held by three hydrogen bonds, and this decreases the probability of gene expression. Methyl groups are added to most bases in the promoter region of a specific gene so that RNA polymerase and its associated proteins will bind more efficiently.

Methyl groups are most often added to cytosines adjacent to guanine bases in or near the promoter sequence, decreasing the probability of gene expression.

Which of the following does not accurately describe events in the movement of mRNA from the nucleus to the cytoplasm? Nuclear pores are large protein complexes that traverse the nuclear membrane and control the inflow and outflow of macromolecules. Processed mRNA transcripts are recognized and transported to the cytoplasm through nuclear pores. Processed mRNA transcripts diffuse passively down their concentration gradient across the nuclear membrane. Primary transcripts must be processed to mRNA before leaving the nucleus.

Processed mRNA transcripts diffuse passively down their concentration gradient across the nuclear membrane.

Small regulatory RNAs are incorporated into a protein complex known as RIL. RISC. REP. RAPD.

RISC

One strand from each of the double-stranded RNA fragments of miRNA or siRNA is incorporated into a protein complex known as: RISC. Xist. RNAi. mRNA. RuBP.

RISC.

How do small regulatory RNAs differ from messenger RNA?

Small regulatory RNAs are not translated into proteins (Chapter 3). As a result, they are often called noncoding RNAs since they do not encode for proteins. Their function is often to regulate the expression of other genes. By contrast, mRNAs are translated into proteins.

Which of the following statements about the methylation state of CpG islands is incorrect? Cells can heavily methylate CpG islands of genes in transposable elements in order to restrict their expression. The methylation state of CpG islands provides a way to turn genes on or off. The methylation state of CpG islands is static and will not change over time. Cells can heavily methylate CpG islands of viral DNA sequences in order to restrict their expression. The methylation state of CpG islands can change in response to the environment.

The methylation state of CpG islands is static and will not change over time.

In female humans and other mammals, dosage compensation is achieved by the inactivation of one of the two X chromosomes in each cell. Which one of the following does not occur in the X-inactivation mechanism of female mammals? When an X chromosome is about to be inactivated, Xist RNA transcripts increase markedly and undergo splicing, but do not encode a protein. Xist is expressed in low levels except when an X chromosome is about to be inactivated. X-inactivation begins with a small region of the X chromosome that contains a gene for an X-inactivation specific transcript (Xist). Xist RNA is attracted to and associates with a protein called the X-chromosome inactivation center (XIC), which becomes entirely coated with Xist. Xist RNA recruits factors that promote DNA methylation, histone modification, and other changes associated with transcriptional silencing.

Xist RNA is attracted to and associates with a protein called the X-chromosome inactivation center (XIC), which becomes entirely coated with Xist.

Sometimes a prokaryotic activator protein interacts with a small molecule in the cell and undergoes a change in shape that alters its affinity for binding to DNA. This change in shape is an example of a(n): allosteric effect. allometric effect. van der Waals effect. isotonic effect. hydrophobic effect.

allosteric effect.

A virus that infects bacteria is called a: temperate virus. lytic virus. lysogenic virus. bacteriophage. microphage.

bacteriophage.

why is glucose preferred over lactose?***

becuase glucose is already broken down and lactose needs to be broken down. which means that glucose is more energy efficient.

The complex of DNA, RNA, and associated proteins that gives shape to the chromosome is called: histones. a scaffold. chromatin. an operon.

chromatin.

The type of gene regulation in which transcription of a gene depends on the presence of a particular combination of enhancers and other regulatory transcription factors is known as: polynomial control. recombinational control. epigenetic control. histone control. combinatorial control.

combinatorial control.

Small regulatory RNAs are thought to have evolved because they: efficiency of DNA repair. fidelity of DNA replication. defense against viruses. likelihood of transcription. speed of translation.

defense against viruses.

All CpG sites located near the promoter region of protein coding genes are methylated. true false

f

Nucleosomes occupy fixed positions along the DNA that remain the same over time and in each cell. true false

f

Primary RNA transcripts are always spliced in the same fashion in order to maintain continuity. true false

f

The miRNA-RISC-mRNA complex enhances the translation efficiency of the mRNA transcript. true false

f

An increase in gene dosage increases the level

of expression because each copy of the gene is regulated independently of other copies - XX females have twice as many X chromosomes as XY males. For genes located in the X chromosome, the dosage of genes is twice as great in females as it is in males. However, the level of expression of X-linked genes is about the same in both sexes.

When a group of functionally related genes located next to one another along the bacterial DNA is transcribed as a single molecule of mRNA, that mRNA is said to be: polyproteinacious. polynomial. polycistronic. polymeric. polytranslational.

polycistronic.

The role of CRP-cAMP is to

provide another level of control of transcription that is more sensitive to the nutritional needs of the cell than the level of control provided by the presence or absence of lactose -The CRP-cAMP complex helps regulate which compounds are utilized. -The concentration of the small molecule cAMP in the cell is a signal about the nutritional state of the cell. In the absence of glucose, cAMP levels are high, and cAMP binds to CRP, changing the shape of CRP so that it can bind at a site near the operator and stimulate binding of RNA polymerase to transcribe lacZ and lacY when lactose is present in the cell. In this way, cAMP is an allosteric activator of CRP binding. However, if lactose is not present in the cell, the lactose repressor binds to the lactose operator and prevents transcription even in the presence of the cAMP-CRP complex.In the presence of glucose, cAMP levels are low, and the cAMP-CRP complex does not bind the lactose operon. As a result, even in the presence of lactose, the lactose operon is not transcribed to high levels (Fig. 19.19b). In this way, E. coli preferentially utilizes glucose when both glucose and lactose are present and utilizes lactose only when glucose is depleted.

gene regulation in eukaryotes

regulation of gene expression occurs through a hierarchy of regulatory mechanisms acting at different levels (and usually at multiple levels) from DNA to protein.

Modification of bases in mRNA transcripts can change the mRNA sequence and thus the characteristics of the protein for which it codes. true false

t

Transcriptional regulation in eukaryotic cells requires the coordinated action of many proteins that interact with one another and with DNA sequences near the gene. true false

t

Untranslated regions of the mRNA transcript may interact with motor proteins to enhance transport of the mRNA to a distinct region of the cell; or these regions may interact with proteins that repress the translation of the mRNA. true false

t

Which of the following does not occur during RNA processing? the addition of a nucleotide cap to the 5′ end of the newly transcribed RNA the addition of a poly(A) tail to the 3′ end of the newly transcribed RNA the removal of all exons during RNA splicing the degradation of excised RNA the removal of all introns during RNA splicing

the removal of all exons during RNA splicing

Insulin is needed to regulate sugar levels in the blood. While every cell in the body contains genes for the production of insulin, it is only produced by a specialized subset of cells in the pancreas. Therefore: every cell must regulate its own sugar production. only the specialized cells of the pancreas have functional genes for insulin production. the genes for insulin production must be mutated except in the specialized cells of the pancreas. there must be mechanisms of gene regulation that promote insulin expression in the specialized pancreatic cells and prevent insulin expression in all other cells. insulin production is not regulated because the genes for it are present in every cell.

there must be mechanisms of gene regulation that promote insulin expression in the specialized pancreatic cells and prevent insulin expression in all other cells.

Some types of small regulatory RNAs are known to be able to inhibit: mutation. replication. translation. recombination.

translation

A functional RISC targets RNA molecules containing one or more regions that can undergo base pairing with the small regulatory RNA contained in the RISC. true false

true

Gene regulation in multicellular organisms leads to differential gene expression and specialized cell functions. true false

true