1In the lac operon of E. coli, which molecule acts as the inducer that inactivates the repressor?
Regulation of Transcription in Prokaryotes: operon models
Easy
A.Glucose
B.cAMP
C.Tryptophan
D.Allolactose
Correct Answer: Allolactose
Explanation:
Allolactose binds to the lac repressor, changing its shape so it can no longer bind the operator, allowing transcription of the lac genes.
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2The lac operon is best described as which type of operon?
Regulation of Transcription in Prokaryotes: operon models
Easy
A.A repressible operon
B.A constitutive operon
C.A non-regulated operon
D.An inducible operon
Correct Answer: An inducible operon
Explanation:
The lac operon is inducible because it is normally off and is switched on (induced) when lactose is present.
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3What is the primary role of the operator sequence in an operon?
Regulation of Transcription in Prokaryotes: operon models
Easy
A.It is the site where RNA polymerase leaves the DNA
B.It codes for the repressor protein
C.It is the DNA site where the repressor protein binds
D.It is the ribosome binding site on mRNA
Correct Answer: It is the DNA site where the repressor protein binds
Explanation:
The operator is a short DNA sequence located near the promoter where a repressor binds to block transcription.
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4A riboswitch is a regulatory element located in which type of molecule?
Regulation of Transcription in Prokaryotes: riboswitches
Easy
A.tRNA
B.DNA
C.mRNA
D.Protein
Correct Answer: mRNA
Explanation:
A riboswitch is a segment of an mRNA molecule that binds a small metabolite and changes its structure to control gene expression.
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5Riboswitches typically regulate gene expression by binding to which of the following?
Regulation of Transcription in Prokaryotes: riboswitches
Easy
A.DNA polymerase
B.Histone proteins
C.Large ribosomal subunits
D.Small metabolite molecules
Correct Answer: Small metabolite molecules
Explanation:
Riboswitches sense the concentration of small metabolites (such as vitamins or amino acids) and adjust gene expression accordingly.
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6The bacteriophage lambda switch controls the decision between which two life cycles?
Regulation of Transcription in Prokaryotes: bacteriophage lambda transcriptional switch
Easy
A.Diploid and haploid
B.Aerobic and anaerobic
C.Lysogenic and lytic
D.Meiotic and mitotic
Correct Answer: Lysogenic and lytic
Explanation:
The lambda transcriptional switch determines whether the phage enters the lytic cycle (making new phage) or the lysogenic cycle (integrating into the host genome).
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7Which protein is essential for maintaining the lysogenic state in bacteriophage lambda?
Regulation of Transcription in Prokaryotes: bacteriophage lambda transcriptional switch
Easy
A.DNA gyrase
B.The Cro protein
C.Lysozyme
D.The CI repressor (lambda repressor)
Correct Answer: The CI repressor (lambda repressor)
Explanation:
The CI repressor maintains lysogeny by repressing the genes needed for the lytic cycle.
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8Which covalent modification of histones is most commonly associated with active gene transcription?
Regulation of Transcription in Eukaryotes: covalent histone modifications
Easy
A.Methylation of DNA
B.Phosphorylation of ribosomes
C.Ubiquitination of mRNA
D.Acetylation
Correct Answer: Acetylation
Explanation:
Histone acetylation loosens chromatin structure, making DNA more accessible and generally promoting transcription.
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9Which enzyme adds acetyl groups to histone proteins?
Regulation of Transcription in Eukaryotes: covalent histone modifications
Easy
A.RNA polymerase
B.DNA methyltransferase
C.Histone deacetylase (HDAC)
D.Histone acetyltransferase (HAT)
Correct Answer: Histone acetyltransferase (HAT)
Explanation:
Histone acetyltransferases (HATs) transfer acetyl groups onto lysine residues of histones, generally increasing transcription.
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10Removal of acetyl groups from histones by HDAC enzymes generally leads to what effect on transcription?
Regulation of Transcription in Eukaryotes: covalent histone modifications
Easy
A.Complete DNA replication
B.Decreased transcription
C.No change in transcription
D.Increased transcription
Correct Answer: Decreased transcription
Explanation:
Histone deacetylases (HDACs) remove acetyl groups, causing chromatin to condense and repressing transcription.
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11Nucleosome remodelling complexes use the energy from which molecule to reposition nucleosomes?
Regulation of Transcription in Eukaryotes: nucleosome remodelling
Easy
A.GTP only
B.Glucose
C.NADH
D.ATP
Correct Answer: ATP
Explanation:
Chromatin remodelling complexes are ATP-dependent; they hydrolyse ATP to slide or displace nucleosomes along DNA.
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12What is the main purpose of nucleosome remodelling?
Regulation of Transcription in Eukaryotes: nucleosome remodelling
Easy
A.To change the accessibility of DNA to transcription factors
B.To synthesize new histone proteins
C.To translate mRNA into protein
D.To replicate the mitochondrial genome
Correct Answer: To change the accessibility of DNA to transcription factors
Explanation:
Nucleosome remodelling repositions or removes nucleosomes to make specific DNA regions more or less accessible to the transcription machinery.
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13In mammals, DNA methylation most commonly occurs on cytosine bases found in which context?
Regulation of Transcription in Eukaryotes: DNA methylation and gene regulation
Easy
A.Poly-A tails
B.CpG dinucleotides
C.AT-rich regions
D.The 5' cap
Correct Answer: CpG dinucleotides
Explanation:
DNA methylation in mammals occurs mainly at cytosines within CpG dinucleotides, often clustered in CpG islands near promoters.
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14Heavy DNA methylation of a gene's promoter region usually results in what?
Regulation of Transcription in Eukaryotes: DNA methylation and gene regulation
Easy
A.Faster translation
B.More mRNA splicing
C.Gene silencing
D.Increased gene expression
Correct Answer: Gene silencing
Explanation:
Methylation of promoter CpG islands typically blocks transcription factor binding and recruits repressive proteins, silencing the gene.
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15What does the abbreviation RISC stand for in RNA interference?
Mechanism of Gene Silencing: RNA interference - RISC-mediated silencing
Easy
A.Ribosomal Initiation Signal Complex
B.RNA-Induced Silencing Complex
C.RNA Integration and Splicing Center
D.Regulatory Intron Silencing Cascade
Correct Answer: RNA-Induced Silencing Complex
Explanation:
RISC stands for RNA-Induced Silencing Complex, the protein complex that uses small RNAs to target and silence mRNAs.
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16Which small RNA molecule is loaded into RISC to guide it to a complementary target mRNA?
Mechanism of Gene Silencing: RNA interference - RISC-mediated silencing
Easy
A.rRNA
B.snoRNA
C.tRNA
D.siRNA
Correct Answer: siRNA
Explanation:
Small interfering RNAs (siRNAs), and also miRNAs, are loaded into RISC and guide the complex to complementary mRNA targets.
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17Which enzyme cleaves long double-stranded RNA into short fragments during RNA interference?
Mechanism of Gene Silencing: mechanisms of RNA interference
Easy
A.Ligase
B.Primase
C.Dicer
D.Helicase
Correct Answer: Dicer
Explanation:
Dicer is an RNase III enzyme that cuts long double-stranded RNA into ~21-nucleotide siRNAs that then enter the RNAi pathway.
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18Heterochromatin is best described as which state of chromatin?
Mechanism of Gene Silencing: role of heterochromatin in gene silencing
Easy
A.A form of single-stranded RNA
B.A ribosomal subunit
C.Tightly packed and transcriptionally inactive
D.Loosely packed and highly active
Correct Answer: Tightly packed and transcriptionally inactive
Explanation:
Heterochromatin is densely condensed chromatin in which genes are generally silenced because the DNA is inaccessible to the transcription machinery.
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19Epigenetic changes are best described as changes that:
Epigenetic Regulation: epigenetics and the environment
Easy
A.Permanently mutate the DNA base sequence
B.Occur only during meiosis
C.Delete entire chromosomes
D.Alter gene expression without changing the DNA sequence
Correct Answer: Alter gene expression without changing the DNA sequence
Explanation:
Epigenetics refers to heritable changes in gene expression that do not involve changes to the underlying DNA sequence, such as DNA methylation and histone modification.
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20Which epigenetic change is commonly seen at the promoters of tumour suppressor genes in cancer cells?
Epigenetic Regulation: epigenetics and cancer
Easy
A.Loss of all histones
B.Hypermethylation
C.Complete gene deletion
D.Increased acetylation
Correct Answer: Hypermethylation
Explanation:
In many cancers, tumour suppressor gene promoters become hypermethylated, silencing these protective genes and contributing to uncontrolled cell growth.
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21In the lac operon, a strain carries a mutation in the operator () on the same DNA molecule as functional structural genes. What phenotype is expected for -galactosidase expression?
Regulation of Transcription in Prokaryotes: operon models
Medium
A.Constitutive expression regardless of lactose
B.Expression only in the presence of glucose
C.Normal inducible expression requiring lactose
D.No expression under any condition
Correct Answer: Constitutive expression regardless of lactose
Explanation:
An (operator constitutive) mutation prevents the repressor from binding. Because the operator acts in cis on the adjacent genes, those structural genes are transcribed constitutively, independent of lactose.
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22The trp operon is regulated by both repression and attenuation. When tryptophan levels are moderate but not saturating, what primarily fine-tunes transcription of the structural genes?
Regulation of Transcription in Prokaryotes: operon models
Medium
A.Binding of CAP-cAMP to the promoter
B.Sigma factor switching by RNA polymerase
C.Inducer exclusion by the tryptophan repressor
D.Attenuation via ribosome stalling at the leader peptide
Correct Answer: Attenuation via ribosome stalling at the leader peptide
Explanation:
Attenuation provides fine control: ribosome position on the trpL leader (dependent on Trp-charged tRNA levels) determines whether a terminator or antiterminator hairpin forms, adjusting transcription beyond the coarse on/off repressor control.
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23Catabolite repression ensures glucose is used before lactose. If a lac operon strain has a mutation abolishing CAP binding, what is the effect when only lactose is present?
Regulation of Transcription in Prokaryotes: operon models
Medium
A.Full constitutive transcription independent of lactose
B.Greatly reduced transcription despite repressor being off
C.Complete loss of any transcription permanently
D.Increased transcription due to loss of negative control
Correct Answer: Greatly reduced transcription despite repressor being off
Explanation:
CAP-cAMP is a positive regulator that boosts RNA polymerase binding at the weak lac promoter. Without functional CAP binding, even when the repressor is released, transcription is inefficient and greatly reduced.
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24A riboswitch controls gene expression by which of the following mechanisms?
Regulation of Transcription in Prokaryotes: riboswitches
Medium
A.Direct binding of a small-molecule metabolite to mRNA, altering its structure
B.Methylation of promoter cytosine residues
C.Binding of a protein repressor to the operator DNA
D.Covalent modification of ribosomal proteins
Correct Answer: Direct binding of a small-molecule metabolite to mRNA, altering its structure
Explanation:
Riboswitches are structured RNA elements, usually in the 5' UTR, that directly bind a metabolite (ligand). Binding triggers a conformational change that controls transcription termination or translation initiation, without any protein factor.
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25In a transcription-terminating riboswitch, binding of the target metabolite typically favors formation of which structure?
Regulation of Transcription in Prokaryotes: riboswitches
Medium
A.A CAP-cAMP activation complex
B.A ribosome-binding site occlusion only
C.An antiterminator that promotes read-through
D.An intrinsic terminator hairpin that halts RNA polymerase
Correct Answer: An intrinsic terminator hairpin that halts RNA polymerase
Explanation:
In many biosynthetic riboswitches (e.g., for FMN or SAM), high metabolite levels stabilize a terminator hairpin, causing premature transcription termination — a negative feedback that shuts off the biosynthetic genes.
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26In the lambda lysis/lysogeny switch, high levels of the cI repressor bound to and produce which outcome?
Regulation of Transcription in Prokaryotes: bacteriophage lambda transcriptional switch
Medium
A.Activation of Cro and entry into the lytic cycle
B.Excision of the prophage from the host chromosome
C.Repression of and activation of , maintaining lysogeny
D.Simultaneous repression of both cI and cro promoters
Correct Answer: Repression of and activation of , maintaining lysogeny
Explanation:
cI dimers occupying and block (silencing lytic genes) while stimulating to sustain cI synthesis. This positive autoregulation locks in the lysogenic state.
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27The lambda switch behaves like a genetic toggle because cI and Cro compete for the same operators. Why does DNA damage (SOS response) shift the switch toward lysis?
Regulation of Transcription in Prokaryotes: bacteriophage lambda transcriptional switch
Medium
A.RecA promotes autocleavage of cI, relieving repression of
B.RecA activates to increase cI levels
C.Host RNA polymerase is inactivated by damage
D.Cro is degraded by activated proteases
Correct Answer: RecA promotes autocleavage of cI, relieving repression of
Explanation:
During the SOS response, activated RecA stimulates cI to self-cleave. Loss of cI derepresses , allowing Cro and lytic genes to be expressed, switching the phage from lysogeny to the lytic cycle.
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28Acetylation of lysine residues on histone tails generally promotes transcription. What is the most direct biochemical reason?
Regulation of Transcription in Eukaryotes: covalent histone modifications
Medium
A.It cross-links adjacent nucleosomes tightly together
B.It adds a bulky group that recruits DNA methyltransferases
C.It directly cleaves the DNA phosphodiester backbone
Correct Answer: It neutralizes positive charges, loosening histone-DNA contacts
Explanation:
Histone acetyltransferases add acetyl groups to lysines, neutralizing their positive charge. This weakens the electrostatic attraction to negatively charged DNA, opening chromatin and also creating docking sites for bromodomain reader proteins.
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29A researcher finds a gene enriched for H3K9me3 (trimethylation of histone H3 lysine 9). What is the likely transcriptional state and reason?
Regulation of Transcription in Eukaryotes: covalent histone modifications
Medium
A.Silenced, because it directly methylates the DNA
B.Silenced, because H3K9me3 recruits HP1 to form heterochromatin
C.Active, because methylation always loosens chromatin
D.Active, because H3K9me3 recruits RNA polymerase II
Correct Answer: Silenced, because H3K9me3 recruits HP1 to form heterochromatin
Explanation:
H3K9me3 is a repressive mark recognized by HP1 (heterochromatin protein 1). HP1 binding spreads condensed heterochromatin, silencing the gene. Unlike acetylation, methylation's effect depends on the specific residue.
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30ATP-dependent chromatin remodelling complexes (e.g., SWI/SNF) regulate transcription primarily by which action?
Regulation of Transcription in Eukaryotes: nucleosome remodelling
Medium
A.Adding methyl groups to histone tails
B.Cleaving histone proteins into fragments
C.Synthesizing new histone octamers
D.Repositioning or ejecting nucleosomes to expose regulatory DNA
Correct Answer: Repositioning or ejecting nucleosomes to expose regulatory DNA
Explanation:
Remodellers use ATP hydrolysis to slide, evict, or restructure nucleosomes. This changes DNA accessibility at promoters and enhancers, allowing or blocking transcription factor and polymerase binding.
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31In mammals, DNA methylation typically occurs at which sequence context and has what usual effect on nearby promoters?
Regulation of Transcription in Eukaryotes: DNA methylation and gene regulation
Medium
A.AT-rich regions; it has no effect on transcription
Cytosine methylation in mammals occurs mainly at CpG sites. Methylation of CpG islands in promoters blocks transcription factor binding and recruits methyl-binding proteins, leading to gene silencing.
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32DNA methylation patterns are heritable through cell division. Which enzyme is chiefly responsible for maintaining methylation on the newly synthesized strand after replication?
Regulation of Transcription in Eukaryotes: DNA methylation and gene regulation
Medium
A.DNMT1, which recognizes hemimethylated CpG sites
B.DNA polymerase, which copies methyl groups directly
C.DNMT3a, which methylates only unmethylated DNA de novo
D.TET enzymes, which remove methyl groups
Correct Answer: DNMT1, which recognizes hemimethylated CpG sites
Explanation:
After replication the parental strand is methylated but the daughter strand is not (hemimethylated). DNMT1, the maintenance methyltransferase, recognizes hemimethylated CpGs and methylates the new strand, preserving the pattern.
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33During RISC-mediated silencing, which component of the complex directly base-pairs with target mRNA to guide cleavage?
Mechanism of Gene Silencing: RNA interference - RISC-mediated silencing
Medium
A.The passenger (sense) strand of the small RNA
B.Both strands of the double-stranded siRNA equally
C.The guide (antisense) strand of the small RNA
D.The Dicer enzyme itself
Correct Answer: The guide (antisense) strand of the small RNA
Explanation:
After the duplex is loaded, the passenger strand is discarded and the guide strand is retained in RISC. It base-pairs with complementary mRNA, directing Argonaute to cleave or repress the target.
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34Perfect complementarity between a small RNA and its mRNA target in RISC typically leads to which outcome, versus imperfect pairing?
Mechanism of Gene Silencing: RNA interference - RISC-mediated silencing
Medium
Perfect base pairing (typical of siRNAs) triggers Argonaute slicer activity, cleaving the mRNA. Imperfect pairing (typical of miRNAs) instead represses translation and promotes deadenylation without direct slicing.
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35Which enzyme processes long double-stranded RNA or pre-miRNA hairpins into ~21–23 nucleotide duplexes during RNA interference?
Mechanism of Gene Silencing: mechanisms of RNA interference
Medium
A.RNA polymerase III
B.Argonaute, a slicer within RISC
C.Dicer, an RNase III-family endonuclease
D.Drosha, which acts only in the nucleus on primary transcripts
Correct Answer: Dicer, an RNase III-family endonuclease
Explanation:
Dicer, an RNase III enzyme, cleaves long dsRNA and pre-miRNA into short duplexes of ~21–23 nt with characteristic 2-nt 3' overhangs. These are then loaded into RISC.
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36In the miRNA pathway, what is the correct order of processing from the primary transcript?
Mechanism of Gene Silencing: mechanisms of RNA interference
Medium
The primary transcript (pri-miRNA) is cropped by Drosha in the nucleus to form pre-miRNA, exported to the cytoplasm, then cleaved by Dicer into the mature miRNA duplex loaded into RISC.
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37Heterochromatin silences genes in part through position-effect variegation. What best explains why a gene relocated near heterochromatin shows patchy (variegated) expression?
Mechanism of Gene Silencing: role of heterochromatin in gene silencing
Medium
A.The gene's DNA sequence is permanently mutated near heterochromatin
B.Stochastic spreading of heterochromatin varies among cells and clonal lineages
C.Only mitochondrial genes are affected by relocation
D.Heterochromatin increases transcription in a random subset of cells
Correct Answer: Stochastic spreading of heterochromatin varies among cells and clonal lineages
Explanation:
Heterochromatin spreads variable distances in different cells and is clonally inherited. In cells where it spreads over the gene, it is silenced; where it does not, the gene is active — producing a mosaic, variegated pattern.
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38In fission yeast, RNAi machinery contributes to heterochromatin formation at centromeres. What is the connection between small RNAs and heterochromatin?
Mechanism of Gene Silencing: role of heterochromatin in gene silencing
Medium
A.Small RNAs directly acetylate histone tails
B.Small RNAs prevent DNA replication at centromeres
C.Small RNAs guide chromatin modifiers to methylate H3K9 at target loci
D.Small RNAs replace histones in the nucleosome core
Correct Answer: Small RNAs guide chromatin modifiers to methylate H3K9 at target loci
Explanation:
The RITS complex uses small RNAs to target nascent centromeric transcripts, recruiting histone methyltransferases that deposit H3K9me. This mark nucleates HP1-based heterochromatin, linking RNAi to transcriptional gene silencing.
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39Studies of the agouti mouse show that maternal diet (e.g., methyl-donor supplementation) alters coat color and disease risk in offspring. What is the epigenetic basis of this effect?
Epigenetic Regulation: epigenetics and the environment
Medium
A.Increased DNA methylation of the agouti gene alters its expression without changing sequence
B.A permanent mutation in the agouti coding sequence
Correct Answer: Increased DNA methylation of the agouti gene alters its expression without changing sequence
Explanation:
Methyl-donor supplementation increases methylation at a transposable element controlling the agouti gene, silencing ectopic expression. The DNA sequence is unchanged, illustrating how environment shapes phenotype epigenetically.
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40A tumor cell shows loss of expression of a tumor-suppressor gene despite an intact coding sequence. Which epigenetic change most commonly explains this in cancer?
Epigenetic Regulation: epigenetics and cancer
Medium
A.Hypermethylation of the gene's promoter CpG island
B.Global hypermethylation across the entire genome
C.Complete loss of all DNA methylation genome-wide
D.Hyperacetylation of the gene's promoter histones
Correct Answer: Hypermethylation of the gene's promoter CpG island
Explanation:
In cancer, tumor-suppressor genes are frequently silenced by localized promoter CpG-island hypermethylation, which blocks transcription without mutating the sequence. This often occurs alongside global genomic hypomethylation.
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41In the lac operon, a mutation in the operator () that abolishes repressor binding is combined in a partial diploid with a wild-type operon on an F' plasmid. The genotype is . In the absence of inducer, which enzymes are constitutively synthesized?
Regulation of Transcription in Prokaryotes: operon models
Hard
A.Both -galactosidase and permease
B.Only -galactosidase (Z)
C.Neither enzyme
D.Only permease (Y)
Correct Answer: Only permease (Y)
Explanation:
acts only in cis. On the chromosome, is defective but is constitutively expressed. On the chromosome, both genes remain repressor-controlled and stay off without inducer. Thus only permease is made constitutively.
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42The trp operon uses attenuation. If a mutation changes the two adjacent tryptophan codons in the leader peptide to two adjacent histidine codons, what is the predicted effect on operon regulation?
Regulation of Transcription in Prokaryotes: operon models
Hard
A.Repressor binding to the operator is enhanced
B.The operon is permanently repressed regardless of amino acid levels
C.Transcription becomes sensitive to histidine rather than tryptophan levels
D.Attenuation is permanently abolished, causing constitutive expression
Correct Answer: Transcription becomes sensitive to histidine rather than tryptophan levels
Explanation:
Attenuation depends on ribosome stalling at the leader-peptide codons when the cognate charged tRNA is scarce. Replacing Trp codons with His codons makes ribosome stalling—and thus antiterminator formation—responsive to histidine availability instead of tryptophan.
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43Many riboswitches contain an aptamer and an expression platform. Consider a transcriptional "OFF" riboswitch that forms an intrinsic terminator when its ligand is bound. Which statement best explains the kinetic requirement for its function?
Regulation of Transcription in Prokaryotes: riboswitches
Hard
A.Ligand binding must occur before RNA polymerase transcribes past the expression platform
B.Ligand binding must occur only after the full mRNA is synthesized
C.Translation initiation must precede ligand binding to the aptamer
D.The aptamer must be located downstream of the terminator hairpin
Correct Answer: Ligand binding must occur before RNA polymerase transcribes past the expression platform
Explanation:
Transcriptional riboswitches are kinetically controlled: the ligand-bound aptamer folds co-transcriptionally to direct formation of the terminator before polymerase reaches the decision point. If polymerase passes first, the choice is locked, so timing is critical.
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44The glmS ribozyme-riboswitch is unusual among riboswitches. What distinguishes its mechanism of controlling gene expression upon ligand binding?
Regulation of Transcription in Prokaryotes: riboswitches
Hard
A.It sequesters the ribosome-binding site via a stable stem-loop only
B.It recruits a repressor protein to the promoter region
C.It methylates its own aptamer domain to block translation
D.It undergoes self-cleavage, using GlcN6P as a coenzyme, degrading its own mRNA
Correct Answer: It undergoes self-cleavage, using GlcN6P as a coenzyme, degrading its own mRNA
Explanation:
The glmS riboswitch is a ribozyme that uses glucosamine-6-phosphate (GlcN6P) as a catalytic cofactor. Ligand binding triggers self-cleavage of the mRNA, targeting it for degradation and shutting down GlmS synthesis—a mechanism distinct from conformational switching alone.
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45In the lambda lysis/lysogeny decision, the cooperative binding of CI repressor to and has a key regulatory consequence. What is it?
Regulation of Transcription in Prokaryotes: bacteriophage lambda transcriptional switch
Hard
A.It recruits Cro to occupy and switch to lysis
B.It represses while activating , maintaining lysogeny
C.It represses while activating , initiating lysis
D.It simultaneously blocks both and transcription
Correct Answer: It represses while activating , maintaining lysogeny
Explanation:
CI bound cooperatively at and blocks (preventing Cro/lytic genes) while CI at contacts RNA polymerase to stimulate , sustaining its own synthesis. This positive autoregulation stabilizes the lysogenic state.
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46During prophage induction following DNA damage, RecA-mediated autocleavage of CI shifts the switch toward lysis. Why does loss of CI at specifically not need to occur first for the switch to flip?
Regulation of Transcription in Prokaryotes: bacteriophage lambda transcriptional switch
Hard
A. binds Cro preferentially even when CI is intact
B. activation requires occupancy by CI
C.CI occupies only at high concentrations, so its cleavage frees before regulation matters
D. has no role in the genetic switch
Correct Answer: CI occupies only at high concentrations, so its cleavage frees before regulation matters
Explanation:
CI binds with high affinity and only when abundant. As CI is cleaved, it dissociates first from the weaker and then , de-repressing . Cro is then transcribed, binds to shut down , and commits the phage to lysis.
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47Trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) can co-occur at "bivalent" domains in embryonic stem cells. What is the functional significance of these bivalent domains?
Regulation of Transcription in Eukaryotes: covalent histone modifications
Hard
A.They recruit DNA polymerase to origins of replication
B.They mark constitutive heterochromatin for permanent silencing
C.They poise developmental genes for rapid activation or repression upon differentiation
D.They target genes for immediate degradation by the proteasome
Correct Answer: They poise developmental genes for rapid activation or repression upon differentiation
Explanation:
Bivalent domains carry the activating H3K4me3 mark alongside the repressive H3K27me3 mark. This keeps developmental regulator genes silent but "poised," so upon differentiation cues one mark is resolved, allowing swift activation or stable repression.
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48The "histone code" hypothesis predicts combinatorial readout of modifications. A protein contains both a bromodomain and a chromodomain in tandem. What binding behavior would this predict?
Regulation of Transcription in Eukaryotes: covalent histone modifications
Hard
A.Simultaneous recognition of an acetylated lysine and a methylated lysine, integrating two marks
B.Recognition of unmodified histone tails only
C.Binding to DNA methylation sites rather than histones
D.Exclusive binding to phosphorylated serine residues
Correct Answer: Simultaneous recognition of an acetylated lysine and a methylated lysine, integrating two marks
Explanation:
Bromodomains read acetyl-lysine and chromodomains read methyl-lysine. A protein with both can engage two distinct modifications at once, providing combinatorial specificity consistent with the histone code and increasing binding avidity and precision.
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49Histone acetylation generally correlates with transcriptional activation. Beyond neutralizing lysine charge, which additional mechanism most directly contributes to this activation?
Regulation of Transcription in Eukaryotes: covalent histone modifications
Hard
A.Acetylation recruits HP1 to compact the nucleosome array
B.Acetyl-lysine creates docking sites recognized by bromodomain-containing remodelers and coactivators
C.Acetylation directly methylates adjacent DNA to open chromatin
D.Acetylation triggers histone degradation, exposing naked DNA
Correct Answer: Acetyl-lysine creates docking sites recognized by bromodomain-containing remodelers and coactivators
Explanation:
Charge neutralization loosens histone–DNA contacts, but acetyl-lysine marks also serve as recruitment platforms. Bromodomain proteins (e.g., in SWI/SNF and TFIID) bind these marks to promote nucleosome remodeling and assembly of the transcription machinery.
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50ATP-dependent chromatin remodelers of the SWI/SNF family and the ISWI family differ functionally. Which contrast is correct?
Regulation of Transcription in Eukaryotes: nucleosome remodelling
Hard
A.Both families methylate CpG islands using ATP
B.SWI/SNF can eject or reposition nucleosomes to expose DNA, while ISWI typically spaces nucleosomes into ordered arrays
C.ISWI ejects nucleosomes to open chromatin, while SWI/SNF only compacts it
D.SWI/SNF requires DNA methylation to function, ISWI does not
Correct Answer: SWI/SNF can eject or reposition nucleosomes to expose DNA, while ISWI typically spaces nucleosomes into ordered arrays
Explanation:
SWI/SNF complexes disrupt, slide, or evict nucleosomes to increase DNA accessibility, often for activation. ISWI-family remodelers primarily generate evenly spaced, regular nucleosome arrays, promoting ordered chromatin and often repression.
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51The histone variant H2A.Z is deposited at nucleosomes flanking promoters. Experiments show its incorporation can both activate and repress genes depending on context. Which best explains this dual role?
Regulation of Transcription in Eukaryotes: nucleosome remodelling
Hard
A.H2A.Z permanently prevents any nucleosome turnover at promoters
B.H2A.Z alters nucleosome stability and creates a labile state that can favor either eviction or stable positioning depending on cofactors
C.H2A.Z directly methylates the promoter DNA to silence genes
D.H2A.Z functions only during DNA replication and has no transcriptional role
Correct Answer: H2A.Z alters nucleosome stability and creates a labile state that can favor either eviction or stable positioning depending on cofactors
Explanation:
H2A.Z changes the biophysical properties of nucleosomes, making them poised. Depending on associated modifications and remodelers, this labile state can facilitate nucleosome eviction (activation) or contribute to stable positioning and repression.
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52In mammals, DNA methylation is maintained through replication by DNMT1 acting on hemimethylated CpG sites. If DNMT1 were selectively inactivated in a dividing cell population, what pattern would be observed over successive divisions?
Regulation of Transcription in Eukaryotes: DNA methylation and gene regulation
Hard
A.Immediate complete demethylation within a single cell cycle
B.Progressive passive loss of methylation, diluting the mark with each round of replication
C.No change, because DNMT3a/b fully maintain methylation
D.Increased de novo methylation compensating for the loss
Correct Answer: Progressive passive loss of methylation, diluting the mark with each round of replication
Explanation:
DNMT1 restores methylation on the newly synthesized strand after replication. Without it, each division leaves one unmethylated daughter strand, so methylation is passively diluted by half each cycle rather than lost instantly. DNMT3a/b establish new marks but do not efficiently maintain them.
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53Methyl-CpG-binding domain proteins (e.g., MeCP2) link DNA methylation to transcriptional repression. Which mechanistic connection is most accurate?
Regulation of Transcription in Eukaryotes: DNA methylation and gene regulation
Hard
A.MeCP2 binds methylated CpGs and recruits histone deacetylase complexes to establish repressive chromatin
B.MeCP2 acetylates histones to open chromatin at methylated sites
C.MeCP2 demethylates DNA to prevent gene silencing
D.MeCP2 directly cleaves methylated DNA to inactivate genes
Correct Answer: MeCP2 binds methylated CpGs and recruits histone deacetylase complexes to establish repressive chromatin
Explanation:
MeCP2 reads 5-methylcytosine and serves as a bridge, recruiting corepressor complexes containing HDACs. Deacetylation of local histones then compacts chromatin, converting the DNA methylation signal into transcriptional silencing.
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54The conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes is a key step in active demethylation. What is the primary fate that ultimately restores unmethylated cytosine?
Regulation of Transcription in Eukaryotes: DNA methylation and gene regulation
Hard
A.Spontaneous reversal of 5hmC back to 5mC without repair
B.Further oxidation to 5fC/5caC followed by base excision repair replacing it with unmodified cytosine
C.Direct enzymatic removal of the methyl group by a demethylase leaving cytosine intact
D.Deamination of 5hmC to uracil incorporated permanently
Correct Answer: Further oxidation to 5fC/5caC followed by base excision repair replacing it with unmodified cytosine
Explanation:
TET enzymes iteratively oxidize 5mC to 5hmC, then 5-formylcytosine and 5-carboxylcytosine. Thymine DNA glycosylase excises 5fC/5caC, and base excision repair inserts an unmodified cytosine, completing active demethylation.
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55In the RISC complex, an Argonaute protein with catalytic "slicer" activity is required for one silencing outcome but dispensable for another. Which pairing is correct?
Mechanism of Gene Silencing: RNA interference - RISC-mediated silencing
Hard
A.Slicer activity is required for both cleavage and repression equally
B.Slicer activity is required for translational repression but not for target cleavage
C.Slicer activity is only needed to unwind the siRNA duplex, not for target action
D.Slicer activity is required for target mRNA cleavage (perfect complementarity) but dispensable for translational repression (miRNA-type mismatched pairing)
Correct Answer: Slicer activity is required for target mRNA cleavage (perfect complementarity) but dispensable for translational repression (miRNA-type mismatched pairing)
Explanation:
Endonucleolytic (slicer) cleavage of target mRNA requires extensive complementarity and catalytic Argonaute. When the guide pairs imperfectly (typical of animal miRNAs), silencing proceeds via translational repression and deadenylation without slicer cleavage.
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56Guide-strand selection during RISC assembly is not random. Which thermodynamic rule predicts which strand of the siRNA duplex is retained as the guide?
Mechanism of Gene Silencing: RNA interference - RISC-mediated silencing
Hard
A.The longer of the two strands becomes the guide regardless of stability
B.The strand whose 5' end sits at the less thermodynamically stable (weaker base-paired) duplex end is chosen as the guide
C.The strand with the more stable 5' end is always chosen as the guide
D.The strand with more GC content at its 3' end becomes the guide
Correct Answer: The strand whose 5' end sits at the less thermodynamically stable (weaker base-paired) duplex end is chosen as the guide
Explanation:
Argonaute loading follows the asymmetry rule: the strand with the less stably paired 5' terminus is preferentially retained as the guide, while the passenger strand is discarded. This thermodynamic bias determines targeting specificity.
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57In some organisms RNAi is amplified and spreads systemically. Which enzymatic activity is essential for signal amplification but absent in mammals, explaining the lack of robust systemic RNAi in mammals?
Mechanism of Gene Silencing: mechanisms of RNA interference
Hard
A.Argonaute, the catalytic core of RISC
B.Dicer, which cleaves long dsRNA into siRNAs
C.Drosha, which processes primary miRNA transcripts
D.RNA-dependent RNA polymerase (RdRP) that synthesizes secondary siRNAs
Correct Answer: RNA-dependent RNA polymerase (RdRP) that synthesizes secondary siRNAs
Explanation:
In C. elegans and plants, RdRP uses target mRNA as a template to generate additional (secondary) siRNAs, amplifying and spreading silencing. Mammals lack canonical RdRP, so their RNAi is not self-amplifying or systemic in the same way.
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58In S. pombe, RNAi contributes to heterochromatin formation at centromeric repeats. Which sequence of events correctly links RNAi to heterochromatin assembly?
Mechanism of Gene Silencing: role of heterochromatin in gene silencing
Hard
A.siRNAs directly methylate centromeric DNA, which then recruits HP1
B.HP1 binds siRNAs first and then recruits DNA methyltransferases to the centromere
C.siRNAs guide the RITS complex to nascent transcripts, recruiting Clr4 to methylate H3K9, creating HP1/Swi6 binding sites
D.siRNAs acetylate H3K9 to open centromeric chromatin
Correct Answer: siRNAs guide the RITS complex to nascent transcripts, recruiting Clr4 to methylate H3K9, creating HP1/Swi6 binding sites
Explanation:
In fission yeast, the RITS complex uses siRNAs to base-pair with nascent centromeric transcripts. This recruits the Clr4 methyltransferase to deposit H3K9me, which is bound by Swi6/HP1, nucleating and spreading heterochromatin in a self-reinforcing loop.
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59Position-effect variegation (PEV) in Drosophila occurs when a gene is relocated near heterochromatin. What does the mosaic (variegated) expression pattern reveal about heterochromatin spreading?
Mechanism of Gene Silencing: role of heterochromatin in gene silencing
Hard
A.The gene is deleted in a random subset of cells, producing patches
B.Heterochromatin spreads a variable distance and is clonally inherited, silencing the gene in some cell lineages but not others
C.Heterochromatin activates the relocated gene stochastically in some cells
D.Heterochromatin uniformly silences the gene in every cell of the organism
Correct Answer: Heterochromatin spreads a variable distance and is clonally inherited, silencing the gene in some cell lineages but not others
Explanation:
PEV shows that heterochromatin spreads a stochastic distance early in development; once established, the silenced or active state is clonally propagated to daughter cells. This produces patches (variegation) of expressing and silenced cells, illustrating epigenetic inheritance.
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60Cancer genomes often display two seemingly opposite DNA methylation changes simultaneously. Which combination and consequence is correct?
Epigenetic Regulation: epigenetics and cancer
Hard
Tumors typically show genome-wide hypomethylation (activating repeats/transposons and fostering instability) together with localized hypermethylation of CpG islands at tumor suppressor promoters, silencing genes like p16 or MLH1. Both contribute to oncogenesis.
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