Gene Regulation and Epigenetics Practice Questions
20 free Gene Regulation and Epigenetics practice questions for the USMLE Step 1. Tap an option to answer — you get instant feedback, the correct answer, and a detailed explanation for every question.
What is the definition of “epigenetics” in the context of gene regulation?
- A Mutations in DNA that change the coding sequence of genes
- B Heritable changes in gene expression not involving DNA sequence change
- C Random fluctuations in gene expression caused by environmental noise
- D Permanent insertion of transposable elements into coding regions
Correct answer: Heritable changes in gene expression not involving DNA sequence change
Epigenetics refers to stable, heritable changes in gene expression without changes in the underlying DNA sequence, typically via chemical modifications to DNA or chromatin that modulate accessibility.
Which chemical modification of DNA is most commonly involved in gene silencing when present in promoter CpG islands?
- A Phosphorylation of cytosine residues
- B Incorporation of uracil in place of thymine
- C Methylation of cytosine bases
- D Acetylation of guanine
Correct answer: Methylation of cytosine bases
Cytosines in CpG dinucleotides are methylated by DNA methyltransferases to give 5-methylcytosine, and dense methylation of a promoter CpG island recruits methyl-CpG binding proteins and histone deacetylases, silencing the gene. Phosphorylation and acetylation are histone rather than base modifications, and uracil in DNA is a lesion that base excision repair removes.
Which family of enzymes is directly responsible for adding methyl groups to DNA during establishment of DNA methylation patterns?
- A Histone deacetylases (HDACs)
- B DNA methyltransferases (DNMTs)
- C RNA polymerases
- D Topoisomerases
Correct answer: DNA methyltransferases (DNMTs)
DNA methyltransferases (DNMTs) catalyze the transfer of methyl groups to cytosine residues (especially at CpG sites), thus establishing DNA methylation, a major epigenetic modification.
Which of the following histone modifications is generally associated with opening chromatin and activating transcription?
- A Dimethylation of histone H3 lysine 9
- B Acetylation of histone H3 and H4 tails
- C Monoubiquitination of histone H2A at lysine 119
- D Trimethylation of histone H3 at lysine 27
Correct answer: Acetylation of histone H3 and H4 tails
Acetylation neutralises the positive charge on histone tail lysines, weakening their grip on the negatively charged DNA backbone and opening chromatin into transcriptionally active euchromatin; bromodomain readers then recruit the transcription machinery. H3K9me2, H3K27me3 and H2AK119 ubiquitination are all repressive marks associated with heterochromatin and Polycomb silencing.
Which histone modification is often correlated with transcriptional repression and formation of heterochromatin?
- A H3K4 trimethylation
- B Histone acetylation
- C H3K9 dimethylation (H3K9me2)
- D Phosphorylation of H3 serine 10
Correct answer: H3K9 dimethylation (H3K9me2)
H3K9me2 is a repressive histone mark associated with tightly packed chromatin (heterochromatin) and transcriptional silencing.
Which non–DNA-altering mechanism can regulate gene expression post-transcriptionally in epigenetic control?
- A Insertion of a transposon within the coding region of the gene
- B MicroRNA-mediated mRNA degradation or translational inhibition
- C Point mutation introduced into the promoter region
- D Deletion of one or more exons from the transcript
Correct answer: MicroRNA-mediated mRNA degradation or translational inhibition
Non-coding RNAs such as microRNAs are part of epigenetic regulation; they bind to mRNAs and cause degradation or block translation, modulating gene expression without altering the DNA sequence.
Which statement best describes how epigenetic modifications influence chromatin structure and gene expression?
- A They change the DNA sequence to switch genes on or off
- B They alter chromatin packaging and DNA accessibility, not sequence
- C They always permanently and irreversibly inactivate a gene
- D They act only transiently during early embryonic development
Correct answer: They alter chromatin packaging and DNA accessibility, not sequence
Epigenetic modifications (DNA methylation, histone modifications, nucleosome remodeling) change chromatin structure and DNA accessibility to the transcription machinery, without altering the underlying DNA sequence.
Which of the following processes is an example of epigenetic regulation in mammals?
- A Single-nucleotide mutation introduced into a coding exon
- B Genomic imprinting expressing only one parental allele
- C Deletion of an entire gene from the chromosome
- D Insertion of a transposable element into the genome
Correct answer: Genomic imprinting expressing only one parental allele
Genomic imprinting is epigenetic: parent-of-origin-specific DNA methylation or chromatin modification leads to expression of only the maternal or paternal allele without changing the DNA sequence.
What is the likely effect of hypermethylation of a tumor suppressor gene promoter in a cancer cell?
- A Increased tumor suppressor expression
- B Stable gene silencing of the tumor suppressor
- C Enhanced DNA repair
- D Splicing of tumor suppressor transcripts
Correct answer: Stable gene silencing of the tumor suppressor
Hypermethylation of promoter CpG islands drives chromatin condensation and transcriptional silencing; when this silences a tumor suppressor gene, loss of its expression can contribute to cancer.
Which enzyme type removes acetyl groups from histone tails, leading to chromatin compaction and gene repression?
- A Histone acetyltransferases (HATs)
- B DNA methyltransferases (DNMTs)
- C Histone deacetylases (HDACs)
- D RNA polymerases
Correct answer: Histone deacetylases (HDACs)
Histone deacetylases (HDACs) remove acetyl groups from histone lysine residues, restoring positive charge, tightening histone-DNA interaction, condensing chromatin, and repressing transcription.
What is chromatin remodeling and why is it important in gene regulation?
- A Changing the DNA base sequence in order to activate genes
- B ATP-dependent repositioning of nucleosomes to change DNA access
- C Deleting stretches of non-coding DNA to shorten chromosomes
- D Repeated replication of the histone protein genes themselves
Correct answer: ATP-dependent repositioning of nucleosomes to change DNA access
Chromatin remodeling is the ATP-dependent movement or restructuring of nucleosomes to open or close chromatin regions, controlling access of the transcription machinery to DNA, a central epigenetic mechanism.
Which of the following statements about histone “code” is most accurate?
- A Only acetylation of histone tails carries any functional significance
- B Patterns of histone tail modifications encode gene-regulatory information
- C Histone modifications permanently rewrite the underlying DNA sequence
- D Histone tail modifications always act to activate gene expression
Correct answer: Patterns of histone tail modifications encode gene-regulatory information
The histone-code hypothesis posits that specific combinations of post-translational histone modifications (acetylation, methylation, etc.) on histone tails create a regulatory language that determines chromatin state and gene expression.
During differentiation of stem cells into a specific tissue type, epigenetic regulation is critical mainly because:
- A It permanently mutates DNA to create tissue-specific gene variants
- B It silences or activates gene sets for that cell type, not the sequence
- C It physically deletes genes irrelevant to the lineage from the genome
- D It increases the overall rate of DNA replication in the cell
Correct answer: It silences or activates gene sets for that cell type, not the sequence
Epigenetic regulation enables stable activation of lineage-specific genes and silencing of irrelevant ones by altering chromatin structure, allowing differentiation without changing the nucleotide sequence.
Which of the following can be considered an epigenetic mechanism that may be influenced by environmental factors such as diet or toxins?
- A DNA point mutation
- B DNA methylation patterns
- C Chromosomal translocation
- D Insertion of a viral genome
Correct answer: DNA methylation patterns
Environmental influences such as diet, toxins, or stress can alter epigenetic mechanisms like DNA methylation or histone modifications, modulating gene expression without changing the DNA sequence.
Which epigenetic mechanism is often reversible and thus a potential target for therapeutic intervention (e.g. in cancer)?
- A DNA sequence mutation
- B DNA methylation and histone modifications
- C Chromosome deletion
- D Gene duplication
Correct answer: DNA methylation and histone modifications
Epigenetic marks such as DNA methylation and histone modifications are reversible and dynamic, making them attractive targets for therapies (e.g. DNMT inhibitors, HDAC inhibitors) in diseases like cancer.
In X-chromosome inactivation in females, which epigenetic mechanism plays a central role in silencing one X chromosome?
- A Widespread histone acetylation across the inactive X chromosome
- B Active DNA demethylation of genes along the inactive X chromosome
- C DNA methylation and heterochromatin formation on the inactive X
- D Point mutations inactivating individual genes on the X chromosome
Correct answer: DNA methylation and heterochromatin formation on the inactive X
X-chromosome inactivation involves widespread DNA methylation and chromatin condensation (heterochromatin formation) of one X chromosome, silencing most of its genes, a classic epigenetic mechanism.
Which of the following describes “genomic imprinting” correctly?
- A Random activation of either the maternal or paternal allele per cell
- B Expression of a gene from one parental allele, the other epigenetically silenced
- C A permanent inherited mutation arising in the expressed allele
- D Somatic recombination occurring between the two parental chromosomes
Correct answer: Expression of a gene from one parental allele, the other epigenetically silenced
Genomic imprinting is an epigenetic phenomenon in which one parental allele is silenced (e.g., by DNA methylation) and only the other is expressed, without changing the DNA sequence.
Which of the following best describes the relationship between DNA methylation and histone modifications in establishing stable gene silencing?
- A They operate fully independently of one another without any crosstalk
- B DNA methylation recruits proteins that draw in histone-modifying enzymes
- C Histone modifications must always be established before DNA methylation
- D Histone modifications act to directly reverse and erase DNA methylation
Correct answer: DNA methylation recruits proteins that draw in histone-modifying enzymes
DNA methylation recruits methyl-CpG-binding proteins that attract histone-modifying enzymes (e.g., deacetylases, methyltransferases), leading to chromatin compaction and stable gene silencing.
Which epigenetic mark would you expect at the promoter region of an actively transcribed housekeeping gene?
- A Dense CpG island methylation paired with H3K9 dimethylation
- B Unmethylated CpG island with histone acetylation
- C High levels of repressive H3K27 trimethylation (H3K27me3)
- D Histone H2A ubiquitination marking transcriptional silencing
Correct answer: Unmethylated CpG island with histone acetylation
Active housekeeping genes typically have unmethylated promoter CpG islands and acetylated histones — creating open chromatin (euchromatin) accessible to transcription machinery.
Which statement correctly describes non-coding RNAs (ncRNAs) in epigenetic regulation?
- A ncRNAs always code for transcription factors that drive transcription
- B ncRNAs recruit chromatin-modifying complexes to specific loci
- C ncRNAs permanently alter the underlying genomic DNA sequence
- D ncRNAs are expressed only in embryonic stem cells during development
Correct answer: ncRNAs recruit chromatin-modifying complexes to specific loci
Non-coding RNAs (like lncRNAs or miRNAs) can guide chromatin-modifying complexes to particular genomic regions, influencing chromatin state and gene expression without altering DNA sequence.