Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (779 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Element, Response; Elements, Response; Response Element.
Where it fits in the MeSH classification
- Broader topics
- Enhancer Elements, Genetic; Promoter Regions, Genetic
- Narrower topics
- Serum Response Element; Vitamin D Response Element; Antioxidant Response Elements
Research landscape
PubMed indexes 10,248 records tagged with the MeSH heading “Response Elements” (counts retrieved 2026-10-29). 749 of them (7.3%) were published from 2020 onward, and the busiest period so far is 2000-2009 with 4,946 records.
Reviews account for 547 records (5.3%) and meta-analyses for 3. Randomized controlled trials number 6 (0.1%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 425 |
| 2000-2009 | 4,946 |
| 2010-2019 | 4,128 |
| 2020 onward | 749 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 547 | 5.3% |
| Meta-analyses | 3 | 0.0% |
| Randomized controlled trials | 6 | 0.1% |
Method: PubMed query "Response Elements"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway | 2020 | Review article Design not recorded in structured metadata | 180 | cc by PMID 32377290 · DOI · PMC7196981 |
| IRES Trans-Acting Factors, Key Actors of the Stress Response | 2019 | Review article Design not recorded in structured metadata | 169 | cc by PMID 30791615 · DOI · PMC6412753 |
| An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases | 2021 | Review article Design not recorded in structured metadata | 149 | cc by PMID 34502501 · DOI · PMC8431732 |
| A single glucocorticoid response element regulates sociability in a sex-specific manner | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 40855007 · DOI · PMC12815654 |
Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases.
- Closing excerpt
- Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (202 words)
The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32377290 · DOI · PMC7196981
IRES Trans-Acting Factors, Key Actors of the Stress Response [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The cellular stress response corresponds to the molecular changes that a cell undergoes in response to various environmental stimuli.
- Closing excerpt
- The impact of ITAFs on the coordinated expression of mRNA families and consequences in cell physiology and diseases are also highlighted.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (204 words)
The cellular stress response corresponds to the molecular changes that a cell undergoes in response to various environmental stimuli. It induces drastic changes in the regulation of gene expression at transcriptional and posttranscriptional levels. Actually, translation is strongly affected with a blockade of the classical cap-dependent mechanism, whereas alternative mechanisms are activated to support the translation of specific mRNAs. A major mechanism involved in stress-activated translation is the internal ribosome entry site (IRES)-driven initiation. IRESs, first discovered in viral mRNAs, are present in cellular mRNAs coding for master regulators of cell responses, whose expression must be tightly controlled. IRESs allow the translation of these mRNAs in response to different stresses, including DNA damage, amino-acid starvation, hypoxia or endoplasmic reticulum stress, as well as to physiological stimuli such as cell differentiation or synapse network formation. Most IRESs are regulated by IRES trans-acting factor (ITAFs), exerting their action by at least nine different mechanisms. This review presents the history of viral and cellular IRES discovery as well as an update of the reported ITAFs regulating cellular mRNA translation and of their different mechanisms of action. The impact of ITAFs on the coordinated expression of mRNA families and consequences in cell physiology and diseases are also highlighted.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30791615 · DOI · PMC6412753
An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Nrf2 is a basic region leucine-zipper transcription factor that plays a pivotal role in the coordinated gene expression of antioxidant and detoxifying enzymes, promoting cell survival in adverse environmental or defective metabolic conditions.
- Closing excerpt
- In this study, we review evidence for the Nrf2/ARE-driven pathway dysfunctions leading to various neurological pathologies, such as Alzheimer's, Parkinson's, and Huntington's diseases, as well as amyotrophic lateral sclerosis, and the beneficial role of natural and synthetic molecules that are able to interact with Nrf2 to enhance its protective efficacy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (197 words)
Nrf2 is a basic region leucine-zipper transcription factor that plays a pivotal role in the coordinated gene expression of antioxidant and detoxifying enzymes, promoting cell survival in adverse environmental or defective metabolic conditions. After synthesis, Nrf2 is arrested in the cytoplasm by the Kelch-like ECH-associated protein 1 suppressor (Keap1) leading Nrf2 to ubiquitin-dependent degradation. One Nrf2 activation mechanism relies on disconnection from the Keap1 homodimer through the oxidation of cysteine at specific sites of Keap1. Free Nrf2 enters the nucleus, dimerizes with small musculoaponeurotic fibrosarcoma proteins (sMafs), and binds to the antioxidant response element (ARE) sequence of the target genes. Since oxidative stress, next to neuroinflammation and mitochondrial dysfunction, is one of the hallmarks of neurodegenerative pathologies, a molecular intervention into Nrf2/ARE signaling and the enhancement of the transcriptional activity of particular genes are targets for prevention or delaying the onset of age-related and inherited neurogenerative diseases. In this study, we review evidence for the Nrf2/ARE-driven pathway dysfunctions leading to various neurological pathologies, such as Alzheimer's, Parkinson's, and Huntington's diseases, as well as amyotrophic lateral sclerosis, and the beneficial role of natural and synthetic molecules that are able to interact with Nrf2 to enhance its protective efficacy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34502501 · DOI · PMC8431732
A single glucocorticoid response element regulates sociability in a sex-specific manner [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Glucocorticoid receptors (GRs) regulate transcription to reduce inflammatory processes, modulate neuron function, and influence behavior.
- Closing excerpt
- Together, these findings demonstrate that GR-induced S1PR3 mitigates inflammatory processes and promotes resilience by reducing coherent neural activity between the LC and mPFC and may be an important mechanism through which the effects of stress in females can be mitigated.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (176 words)
Glucocorticoid receptors (GRs) regulate transcription to reduce inflammatory processes, modulate neuron function, and influence behavior. However, the precise loci bound by GRs that are critically important for these effects have not been fully determined. Here, we deleted the GR binding site near the sphingosine-1-phosphate receptor 3 (S1PR3) gene using a CRISPR/Cas9 approach in rats (S1PR3GRE-/GRE- rats). Socially defeated S1PR3GRE-/GRE- males displayed increased inflammatory markers and reduced sociability compared to defeated wild-type (WT) controls. Similar effects were observed in non-stressed females, indicating a greater dependence on the regulation of S1PR3 by GRs in females. Coherent neural activity between the locus coeruleus (LC) and medial prefrontal cortex (mPFC) was increased in defeated S1PR3GRE-/GRE- males whereas increases were observed in non-stressed S1PR3GRE-/GRE females. Chemogenetically inhibiting mPFC-projecting LC neurons during defeat increased subsequent social interaction in WT and S1PR3GRE-/GRE- males. Together, these findings demonstrate that GR-induced S1PR3 mitigates inflammatory processes and promotes resilience by reducing coherent neural activity between the LC and mPFC and may be an important mechanism through which the effects of stress in females can be mitigated.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40855007 · DOI · PMC12815654
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article The Human Transcription Factors [5]
- Research article The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress [6]
- Research article Nrf2 signaling in coordinated activation of antioxidant gene expression [7]
- Research article Regulatory mechanisms controlling gene expression mediated by the antioxidant response element [8]
- Research article Estrogen receptor interaction with estrogen response elements [9]
- Research article The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB [10]
References
- Hassanein EHM, Sayed AM, Hussein OE, Mahmoud AM. Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway. . 2020. PMID 32377290 · DOI · PMC7196981
- Godet AC, David F, Hantelys F, Tatin F, Lacazette E, Garmy-Susini B, et al.. IRES Trans-Acting Factors, Key Actors of the Stress Response. . 2019. PMID 30791615 · DOI · PMC6412753
- Zgorzynska E, Dziedzic B, Walczewska A. An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases. . 2021. PMID 34502501 · DOI · PMC8431732
- Corbett BF, Arner J, Luz S, Yan J, Castro-Vildosola J, Hala T, et al.. A single glucocorticoid response element regulates sociability in a sex-specific manner. . 2026. PMID 40855007 · DOI · PMC12815654
- Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y, Albu M, et al.. The Human Transcription Factors. Cell. 2018. PMID 29425488 · DOI · PMC12908702
- Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009. PMID 19182219 · DOI · PMC2679427
- Jaiswal AK. Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med. 2004. PMID 15110384 · DOI
- Nguyen T, Sherratt PJ, Pickett CB. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol. 2003. PMID 12359864 · DOI
- Klinge CM. Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res. 2001. PMID 11452016 · DOI
- Kandel ER. The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain. 2012. PMID 22583753 · DOI · PMC3514210
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.