Introduction: Transcription factor-regulated receptors are central to pharmacology and gene regulation, linking extracellular signals to changes in receptor expression and function. This topic covers ligand-activated nuclear receptors (eg, steroid, thyroid, PPAR), DNA response elements, transcription factors (STATs, NF-κB, AP-1), co‑activators and co‑repressors, chromatin remodeling, and post‑translational modifications that modulate receptor transcription. Understanding receptor gene regulation, promoter architecture, and receptor–transcription factor interactions is essential for drug design, selective modulators (SERMs), and predicting therapeutic responses. These concepts are directly relevant to B. Pharm students studying pharmacodynamics, molecular pharmacology, and drug discovery. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is a classical feature of ligand-activated nuclear receptors that allows them to regulate gene transcription directly?
- G-protein coupling domain
- Protease activation site
- Distinct DNA-binding domain with zinc finger motifs
- Ion channel pore-forming region
Correct Answer: Distinct DNA-binding domain with zinc finger motifs
Q2. Which element on DNA is specifically recognized by nuclear receptors to modulate target gene transcription?
- TATA box
- Hormone response element (HRE)
- Polyadenylation signal
- Enhancer RNA sequence
Correct Answer: Hormone response element (HRE)
Q3. Which co‑activator protein is commonly recruited by ligand-bound nuclear receptors to enhance transcription through histone acetylation?
- NCoR
- HDAC1
- SRC-1 (steroid receptor coactivator-1)
- SMRT
Correct Answer: SRC-1 (steroid receptor coactivator-1)
Q4. A selective estrogen receptor modulator (SERM) acts as an agonist in some tissues and antagonist in others. This tissue-selective activity is largely due to which mechanism?
- Differences in receptor ligand-binding pocket sequence across tissues
- Tissue-specific expression of co-activators and co-repressors
- SERM irreversible covalent binding to DNA
- Variation in membrane permeability of SERM molecules
Correct Answer: Tissue-specific expression of co-activators and co-repressors
Q5. Which transcription factor family is typically activated by cytokine receptors and directly binds DNA as a dimer after phosphorylation?
- NF-κB
- STAT (Signal Transducer and Activator of Transcription)
- CREB
- Heat-shock factors (HSF)
Correct Answer: STAT (Signal Transducer and Activator of Transcription)
Q6. How does phosphorylation of a transcription factor commonly affect receptor gene expression?
- Always causes protein degradation and reduces expression
- Prevents DNA binding permanently
- Alters transcription factor activity, localization, or interaction with co-factors
- Converts receptors into ion channels
Correct Answer: Alters transcription factor activity, localization, or interaction with co-factors
Q7. Which assay is most appropriate to demonstrate in vivo binding of a transcription factor to a receptor gene promoter?
- Western blot
- Chromatin immunoprecipitation (ChIP)
- ELISA for receptor protein level
- Patch-clamp recording
Correct Answer: Chromatin immunoprecipitation (ChIP)
Q8. Nuclear receptor heterodimerization with RXR (retinoid X receptor) typically affects transcription how?
- Blocks DNA binding entirely
- Allows recognition of different response element spacing and modulates transcriptional activity
- Targets the complex for proteasomal degradation
- Causes immediate receptor internalization
Correct Answer: Allows recognition of different response element spacing and modulates transcriptional activity
Q9. Which domain of a nuclear receptor is primarily responsible for ligand specificity and interaction with co-regulators?
- DNA-binding domain (DBD)
- Ligand-binding domain (LBD)
- Transmembrane domain
- Catalytic kinase domain
Correct Answer: Ligand-binding domain (LBD)
Q10. Which class of drugs directly targets nuclear receptors to alter gene transcription and is commonly used in metabolic disorders?
- Proton pump inhibitors
- PPAR agonists (e.g., fibrates, thiazolidinediones)
- Beta-lactam antibiotics
- ACE inhibitors
Correct Answer: PPAR agonists (e.g., fibrates, thiazolidinediones)
Q11. NF-κB regulates many receptor genes in inflammation. Which event typically activates NF-κB signaling?
- Dephosphorylation of IκB leading to nuclear export
- Proteasomal degradation of IκB releasing NF-κB to enter the nucleus
- Direct binding of NF-κB to membrane receptors
- Formation of RNA polymerase II holoenzyme
Correct Answer: Proteasomal degradation of IκB releasing NF-κB to enter the nucleus
Q12. Which technique would you use to measure transcriptional activation of a receptor promoter by a transcription factor in cultured cells?
- Reporter gene assay (luciferase)
- Mass spectrometry of receptor protein
- Flow cytometry for cell surface receptors
- Transmission electron microscopy
Correct Answer: Reporter gene assay (luciferase)
Q13. Which statement best describes orphan nuclear receptors in pharmacology?
- They are nuclear receptors with no known endogenous ligands initially identified
- They are receptors exclusively found in bacteria
- They lack a DNA-binding domain
- They are membrane ion channels mistaken for receptors
Correct Answer: They are nuclear receptors with no known endogenous ligands initially identified
Q14. How can epigenetic modifications influence transcription factor-regulated receptor expression?
- They change the receptor amino acid sequence
- They modify chromatin accessibility via DNA methylation and histone modification, affecting transcription factor binding
- They directly alter ligand chemical structure
- They only affect post-translational receptor trafficking
Correct Answer: They modify chromatin accessibility via DNA methylation and histone modification, affecting transcription factor binding
Q15. Which domain in basic helix-loop-helix (bHLH) transcription factors mediates dimerization and DNA binding relevant to receptor gene regulation?
- Transmembrane helix
- bHLH domain
- SH2 domain
- Pleckstrin homology domain
Correct Answer: bHLH domain
Q16. What role do co-repressors such as NCoR and SMRT play in receptor gene regulation?
- They acetylate histones to enhance transcription
- They recruit histone deacetylases to suppress transcription
- They act as membrane anchors for receptors
- They catalyze receptor dimerization
Correct Answer: They recruit histone deacetylases to suppress transcription
Q17. Which property distinguishes type I nuclear receptors (eg, steroid receptors) from type II (eg, thyroid receptor) in terms of cellular localization before ligand binding?
- Type I are typically cytoplasmic and translocate to the nucleus upon ligand binding; type II are often nuclear bound to DNA even without ligand
- Type I are permanently membrane-bound; type II are mitochondrial
- Type I lack a DNA-binding domain; type II have no ligand-binding domain
- Type I receptors are only in plants; type II only in animals
Correct Answer: Type I are typically cytoplasmic and translocate to the nucleus upon ligand binding; type II are often nuclear bound to DNA even without ligand
Q18. In drug discovery, which approach leverages knowledge of transcription factor-regulated receptors to find selective modulators?
- High-throughput screening of compounds using cell-based reporter assays for receptor transcriptional activity
- Measuring compound volatility only
- Testing compounds on bacterial cultures lacking receptors
- Using only in silico solubility prediction without biological assays
Correct Answer: High-throughput screening of compounds using cell-based reporter assays for receptor transcriptional activity
Q19. Which transcription factor is rapidly activated by cAMP signaling and binds CRE (cAMP response element) to regulate genes including some receptor genes?
- NFAT
- CREB (cAMP response element-binding protein)
- HIF-1α
- p53
Correct Answer: CREB (cAMP response element-binding protein)
Q20. How can microRNAs influence transcription factor-regulated receptor expression?
- By degrading receptor DNA sequences
- By post-transcriptionally downregulating receptor mRNA or transcription factor mRNA, altering protein levels
- By phosphorylating transcription factors directly
- By converting transcription factors into enzymes
Correct Answer: By post-transcriptionally downregulating receptor mRNA or transcription factor mRNA, altering protein levels
Q21. Which receptor family member is a classic example of a ligand-activated transcription factor that heterodimerizes with RXR and regulates lipid metabolism?
- Beta-adrenergic receptor
- Peroxisome proliferator-activated receptor (PPAR)
- Toll-like receptor
- NMDA receptor
Correct Answer: Peroxisome proliferator-activated receptor (PPAR)
Q22. Which post-translational modification of histones is generally associated with active transcription of receptor genes?
- Histone deacetylation
- Histone methylation at H3K27 (tri-methylation)
- Histone acetylation (eg, H3K9ac)
- DNA strand cleavage
Correct Answer: Histone acetylation (eg, H3K9ac)
Q23. Which experimental technique identifies DNA sequences bound by a transcription factor in vitro via mobility shifts?
- EMSA (electrophoretic mobility shift assay)
- Southern blot
- FRET
- Northern blot
Correct Answer: EMSA (electrophoretic mobility shift assay)
Q24. In the context of receptor gene regulation, what is a promoter proximal element?
- A membrane lipid that binds receptors
- A DNA sequence located near the transcription start site that influences transcription factor binding
- A small peptide that degrades transcription factors
- A cytosolic enzyme that phosphorylates receptors
Correct Answer: A DNA sequence located near the transcription start site that influences transcription factor binding
Q25. Which transcription factor complex formed by Fos and Jun regulates expression of genes including some receptors and is known as AP-1?
- NF-κB complex
- AP-1 (Activator Protein-1)
- SP1 complex
- CREB-ATF complex
Correct Answer: AP-1 (Activator Protein-1)
Q26. A mutation in a receptor gene promoter reduces binding of a transcriptional repressor, leading to increased receptor expression. This is an example of which regulatory mechanism?
- Post-translational modification
- Loss of cis-regulatory element function
- Alternative splicing
- Protein ubiquitination
Correct Answer: Loss of cis-regulatory element function
Q27. Which of the following best describes how hormone-bound glucocorticoid receptor regulates target genes?
- It remains in the cytoplasm and blocks translation
- It translocates to the nucleus, binds GREs (glucocorticoid response elements), and recruits co-regulators to modulate transcription
- It becomes a membrane ion channel
- It degrades mRNA directly in the cytosol
Correct Answer: It translocates to the nucleus, binds GREs (glucocorticoid response elements), and recruits co-regulators to modulate transcription
Q28. Which pharmacological strategy exploits transcription factor-regulated receptors to reduce pathological gene expression in cancer?
- Use of kinase inhibitors only with no effect on transcription
- Development of receptor antagonists or selective modulators that alter transcriptional programs
- Administration of broad-spectrum antibiotics
- Increasing dietary sugar to modulate expression
Correct Answer: Development of receptor antagonists or selective modulators that alter transcriptional programs
Q29. Which factor is important when designing small-molecule modulators targeting nuclear receptor ligand-binding domains?
- Ability to crosslink DNA strands
- Shape complementarity, affinity for LBD, and influence on receptor conformation to recruit co-regulators
- Capacity to phosphorylate histones
- Non-specific membrane disruption
Correct Answer: Shape complementarity, affinity for LBD, and influence on receptor conformation to recruit co-regulators
Q30. Why is understanding transcription factor-regulated receptor expression critical for predicting drug response and adverse effects?
- Because receptors never change expression after birth
- Because receptor levels, isoforms, and co-regulator context determine drug efficacy, selectivity, and tissue-specific adverse effects
- Because transcription factors directly metabolize drugs
- Because it only affects taste perception of drugs
Correct Answer: Because receptor levels, isoforms, and co-regulator context determine drug efficacy, selectivity, and tissue-specific adverse effects
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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