GO:0023019 signal transduction involved in regulation of gene expression: Signaling to Gene Expression, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0023019 describes any process that modulates the frequency, rate or extent of gene expression as a consequence of a signal being released and/or conveyed from one location to another [1, 3].
• The term bridges signal transduction and transcriptional control, covering pathways such as estrogen receptor signaling, Wnt/beta-catenin signaling, and glucose-responsive gene regulation [1, 3, 7].
• Key molecular players include steroid hormone receptors (ESR1), Wnt pathway components (CTNNB1, APC), metabolic sensors (ChREBP, SREBP), and stress-responsive transcription factors (NFE2L2) [1, 3, 4, 7].
• Dysregulation of signal-to-gene-expression coupling underlies cancer, metabolic disorders, and inflammatory diseases [1, 3, 4].
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable causal dissection of signaling nodes that control gene expression.
• Understanding GO:0023019 is essential for interpreting how environmental and intrinsic signals are integrated at the genome level.
Description
Signal transduction involved in regulation of gene expression (GO:0023019) is a biological process that encompasses any mechanism by which a signal, released or conveyed from one location to another, modulates the frequency, rate, or extent of gene expression [1, 3]. This term captures the essential link between extracellular or intracellular cues and the transcriptional or post-transcriptional output of the genome. It is distinct from general signal transduction because its defining outcome is a change in gene expression, not merely a change in cellular state or enzyme activity [1, 4]. Researchers study this process to understand how cells adapt to hormones, growth factors, nutrients, and stress, and how these adaptations go awry in disease [1, 3, 7]. The importance of GO:0023019 spans endocrinology, developmental biology, immunology, and cancer research. For example, estrogen receptor signaling directly regulates target gene transcription in breast tissue, and its dysregulation is a hallmark of hormone-dependent cancers. Similarly, Wnt/beta-catenin signaling controls developmental gene programs, and mutations in this pathway drive colorectal cancer and other malignancies. Metabolic signals such as glucose availability also feed into gene expression networks, influencing insulin sensitivity and metabolic disease. Because GO:0023019 integrates signal perception with gene regulation, it is a focal point for experimental strategies that perturb signaling components and measure transcriptional consequences. Modern CRISPR-based tools allow precise knockout, point mutation, knock-in, and overexpression of signaling genes, enabling researchers to establish causal relationships between specific signals and gene expression outcomes. This article provides a research-grade overview of GO:0023019, including its definition, core mechanisms, key genes, disease relevance, and experimental methods.
signal transduction involved in regulation of gene expression At A Glance
| GO ID | GO:0023019 |
|---|---|
| GO term | signal transduction involved in regulation of gene expression |
| Ontology | biological_process |
| Synonym | regulation of gene expression as a consequence of signal transmission |
| Major function | Coupling of signal perception and transmission to changes in gene expression frequency, rate, or extent |
| Definition source | QuickGO |
| Related processes | Estrogen receptor signaling, Wnt/beta-catenin signaling, glucose regulation of gene expression, oxidative stress response |
| Key effectors | Transcription factors, nuclear receptors, coactivators/corepressors, signaling kinases |
| Disease relevance | Cancer, metabolic disorders, inflammatory diseases, developmental defects |
What Is GO:0023019?
GO:0023019, signal transduction involved in regulation of gene expression, is defined as any process that modulates the frequency, rate or extent of gene expression as a consequence of a process in which a signal is released and/or conveyed from one location to another. In simpler terms, it is the flow of information from a signaling event to a change in how much or how often a gene is expressed. This includes signals that originate outside the cell (e.g., hormones, growth factors) or inside the cell (e.g., metabolic intermediates, stress signals) and ultimately alter transcription, mRNA stability, or translation. The synonym 'regulation of gene expression as a consequence of signal transmission' emphasizes the dependency on signal conveyance.
Why Is signal transduction involved in regulation of gene expression Important in Cell Biology?
GO:0023019 is critically important because it explains how cells convert dynamic signals into stable changes in gene expression programs. This process underlies normal development, tissue homeostasis, and adaptive responses to environmental changes, and its dysregulation is a common theme in cancer, metabolic disease, and chronic inflammation [1, 3, 4, 7]. By studying this term, researchers can identify the precise signaling nodes that control disease-associated gene expression and design targeted interventions.
• Provides a mechanistic framework for understanding how hormones, growth factors, and nutrients control gene expression [1, 3, 7].
• Explains the integration of environmental signals with the genome, as described in epigenetic regulation.
• Is essential for developmental processes, including cell fate specification and tissue patterning.
• Dysregulation contributes to cancer, particularly hormone-dependent and Wnt-driven tumors [1, 3].
• Plays a role in metabolic adaptation, including glucose-responsive gene expression.
• Involved in oxidative stress responses through NFE2L2/KEAP1 signaling.
• Relevant to bacterial regulatory systems under respiration-inhibitory conditions.
• Contributes to ion channel expression regulation in excitable cells.
• Plant GRAS gene family members participate in signal transduction for stress resistance and symbiosis.
• Offers therapeutic targets for modulating gene expression in disease [1, 3, 4].
What Happens During signal transduction involved in regulation of gene expression?
Signal Perception and Transmission
In simple terms: A signal is received and passed along inside the cell.
The process begins when a signal, such as a hormone or growth factor, is released from one location and conveyed to a target cell. For example, estrogen binds to estrogen receptors (ESR1/ESR2), triggering receptor dimerization and translocation to the nucleus. Similarly, Wnt ligands bind to Frizzled receptors and LRP co-receptors, leading to stabilization of beta-catenin (CTNNB1). These events represent the signal transmission phase that precedes gene expression changes.
Signal Integration and Transcription Factor Activation
In simple terms: The signal activates proteins that turn genes on or off.
Once transmitted, signals converge on transcription factors and co-regulators. Estrogen-bound ESR1 recruits coactivators to estrogen response elements in target gene promoters. In the Wnt pathway, stabilized beta-catenin enters the nucleus and partners with TCF/LEF transcription factors to activate Wnt target genes. Metabolic signals such as glucose can activate ChREBP or SREBP, which then regulate lipogenic and glycolytic gene expression. These integration steps determine the specificity and magnitude of the transcriptional response.
Chromatin Remodeling and Epigenetic Modulation
In simple terms: The cell's DNA packaging is altered to allow or block gene expression.
Signal-induced transcription factors often recruit chromatin-modifying enzymes that alter histone acetylation, methylation, or DNA methylation, thereby changing gene accessibility. This epigenetic layer integrates intrinsic and environmental signals to shape gene expression outcomes. For instance, estrogen receptor signaling can recruit histone acetyltransferases to open chromatin at target loci.
Transcriptional Output and Feedback
In simple terms: Genes are turned on or off, and the cell responds.
The ultimate outcome is a change in the frequency, rate, or extent of gene expression. This can include increased transcription of metabolic enzymes, ion channels, or stress-response genes. For example, NFE2L2 (Nrf2) activation by oxidative stress leads to upregulation of heme oxygenase-1 (HMOX1) and other antioxidant genes. In excitable cells, oncogenes and signaling pathways regulate Na+ channel expression. Feedback mechanisms, such as induction of negative regulators, ensure transient responses.
Key Genes Involved in GO:0023019 signal transduction involved in regulation of gene expression
The following genes and proteins are central to signal transduction involved in regulation of gene expression, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ESR1 | Estrogen receptor alpha; mediates estrogen-dependent gene transcription | Breast cancer, hormone therapy resistance |
| ESR2 | Estrogen receptor beta; modulates estrogen signaling | Endocrine disorders, cancer |
| CTNNB1 | Beta-catenin; key effector of Wnt signaling that activates TCF/LEF target genes | Colorectal cancer, developmental defects |
| APC | Negative regulator of Wnt/beta-catenin signaling | Colorectal cancer, familial adenomatous polyposis |
| NFE2L2 | Nrf2; transcription factor activated by oxidative stress to induce antioxidant genes | Inflammation, cancer chemoprevention |
| KEAP1 | Negative regulator of Nrf2; targets Nrf2 for degradation | Oxidative stress-related diseases |
| HMOX1 | Heme oxygenase-1; antioxidant enzyme induced by Nrf2 signaling | Inflammation, cardiovascular disease |
| ChREBP | Carbohydrate-responsive element-binding protein; mediates glucose-induced gene expression | Metabolic syndrome, diabetes |
| SREBP | Sterol regulatory element-binding protein; regulates lipid metabolism genes | Dyslipidemia, fatty liver disease |
| GRAS family | Plant transcription factors involved in signal transduction for growth and stress responses | Plant biology, crop improvement |
| SCN9A | Sodium channel, voltage-gated, type IX alpha subunit; expression regulated by oncogenes and signaling | Pain disorders, epilepsy |
| SCN1A | Sodium channel, voltage-gated, type I alpha subunit; regulated by signaling pathways | Epilepsy, migraine |
| MYC | Oncogene; transcription factor that amplifies gene expression programs | Cancer |
| RAS | Small GTPase; transmits growth signals to downstream effectors | Cancer, developmental disorders |
| MAPK1 | Extracellular signal-regulated kinase 2; relays signals to transcription factors | Cancer, inflammation |
| CREB1 | cAMP response element-binding protein; mediates signal-induced transcription | Neurodegeneration, cancer |
| NFKB1 | NF-kappa-B p105 subunit; central mediator of inflammatory gene expression | Inflammation, cancer |
How Is signal transduction involved in regulation of gene expression Regulated?
The process of signal transduction involved in regulation of gene expression is itself tightly regulated at multiple levels. Negative feedback loops, such as KEAP1-mediated degradation of NFE2L2, prevent excessive antioxidant gene expression. In the Wnt pathway, APC and AXIN promote beta-catenin degradation in the absence of signal, ensuring low basal transcription. Estrogen receptor activity is modulated by phosphorylation, cofactor recruitment, and ligand availability. Metabolic signals such as glucose and insulin regulate ChREBP and SREBP activity, linking nutrient status to gene expression. Additionally, epigenetic mechanisms, including DNA methylation and histone modification, provide a layer of regulation that integrates intrinsic and environmental signals.
signal transduction involved in regulation of gene expression and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ESR1 | Breast cancer, endocrine resistance | Knockout or point mutation in MCF-7 cells |
| CTNNB1 | Colorectal cancer, developmental defects | Knock-in of oncogenic beta-catenin in HCT116 cells |
| NFE2L2 | Oxidative stress-related diseases, cancer | Knockout or overexpression in A549 cells |
| ChREBP | Type 2 diabetes, fatty liver disease | Knockout in HepG2 cells |
| SCN1A | Epilepsy, migraine | Point mutation knock-in in iPSC-derived neurons |
Cancer
Dysregulated signal transduction to gene expression is a hallmark of cancer. Estrogen receptor signaling drives proliferation in breast cancer, and mutations in ESR1 can confer resistance to endocrine therapy. Aberrant Wnt/beta-catenin signaling, often due to APC mutations, leads to constitutive activation of oncogenic gene programs in colorectal cancer. Oxidative stress signaling through NFE2L2/KEAP1 is frequently altered in lung and other cancers, affecting chemoresistance.
Metabolic Disorders
Glucose and lipid signals directly regulate gene expression through ChREBP and SREBP, and their dysregulation contributes to insulin resistance, type 2 diabetes, and non-alcoholic fatty liver disease. Understanding these pathways is critical for developing therapies that target metabolic gene expression.
Inflammatory and Oxidative Stress Diseases
NFE2L2/KEAP1 signaling controls antioxidant and anti-inflammatory gene expression. Impaired Nrf2 activation is associated with chronic inflammatory diseases and neurodegeneration, while constitutive activation can promote tumor survival.
Neurological and Channelopathies
Oncogenes and signal transduction pathways regulate Na+ channel expression in neurons and muscle, and their dysregulation is linked to epilepsy, pain disorders, and other channelopathies.
From signal transduction involved in regulation of gene expression-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of ESR1 abolish estrogen-induced gene expression? | ESR1 knockout cell line (e.g., MCF-7) |
| Does a specific point mutation in CTNNB1 stabilize beta-catenin and activate Wnt targets? | CTNNB1 point mutation knock-in (e.g., S33Y) |
| Can overexpression of NFE2L2 drive antioxidant gene expression? | NFE2L2 overexpression in HEK293T cells |
| Does a tagged knock-in of ChREBP reveal its genomic binding sites? | ChREBP-HA knock-in in HepG2 cells |
| Does knockout of KEAP1 constitutively activate Nrf2 target genes? | KEAP1 knockout in A549 cells |
| Does a point mutation in SCN1A alter channel expression? | SCN1A point mutation knock-in in iPSC-derived neurons |
How to Study the signal transduction involved in regulation of gene expression Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global mRNA levels | Identify differentially expressed genes after signal perturbation [1, 3] |
| ChIP-seq | Genome-wide transcription factor binding | Map ESR1 or beta-catenin binding sites [1, 3] |
| ATAC-seq | Chromatin accessibility | Assess signal-induced chromatin opening |
| Proteomics | Protein abundance and modifications | Quantify signaling pathway components |
| Phosphoproteomics | Phosphorylation events | Identify kinase cascades activated by signals |
| Luciferase reporter assay | Transcriptional activity of a promoter | Measure signal-induced gene expression |
| Live-cell imaging | Dynamics of transcription factor localization | Visualize signal transduction in real time |
Transcriptomic Profiling (RNA-seq)
RNA sequencing measures global changes in gene expression following signal perturbation. It is widely used to identify target genes of signaling pathways such as estrogen receptor or Wnt/beta-catenin [1, 3]. By comparing wild-type and knockout cells, researchers can define the gene expression program controlled by a specific signaling node.
Chromatin Immunoprecipitation (ChIP-seq)
ChIP-seq identifies genome-wide binding sites of transcription factors and cofactors, revealing how signals direct transcriptional complexes to specific loci. For example, ChIP-seq for ESR1 or beta-catenin has mapped their target enhancers and promoters [1, 3].
Proteomics and Phosphoproteomics
Mass spectrometry-based proteomics quantifies protein abundance and post-translational modifications, providing a systems-level view of signaling events that lead to gene expression changes. This is particularly useful for capturing kinase cascades and feedback loops.
Reporter Assays and Imaging
Luciferase reporters driven by signal-responsive promoters allow real-time monitoring of gene expression changes. Live-cell imaging of fluorescently tagged transcription factors or nascent RNA can reveal the dynamics of signal-to-expression coupling.
How CRISPR Can Be Used to Study GO:0023019 signal transduction involved in regulation of gene expression
Knockout
CRISPR knockout is used to delete genes encoding signaling components, such as ESR1, CTNNB1, or NFE2L2, to determine their necessity for signal-induced gene expression. For example, ESR1 knockout in breast cancer cells abolishes estrogen-dependent transcription. Knockout of KEAP1 leads to constitutive Nrf2 activation, demonstrating its role as a negative regulator.
Point Mutation
Point mutations can mimic disease-associated variants or activate/inactivate signaling proteins. For instance, introducing the S33Y mutation in CTNNB1 stabilizes beta-catenin and constitutively activates Wnt target genes. Point mutations in ESR1 (e.g., Y537S) are linked to endocrine resistance and can be modeled to study gene expression changes.
Knock-in
Knock-in of tags (e.g., HA, GFP) or reporter cassettes allows tracking of endogenous signaling proteins and their transcriptional targets. A ChREBP-HA knock-in enables ChIP-seq to map glucose-responsive binding sites. Knock-in of luciferase reporters downstream of signal-responsive promoters provides a sensitive readout of gene expression.
Overexpression
Overexpression of signaling genes, such as NFE2L2 or constitutively active CTNNB1, is used to test sufficiency for gene expression changes. Overexpression of Nrf2 in HEK293T cells induces antioxidant genes like HMOX1. This approach complements loss-of-function studies to establish causality.
How EDITGENE Supports signal transduction involved in regulation of gene expression Research
Researchers studying signal transduction involved in regulation of gene expression-related genes often need to determine whether a candidate gene is causally involved in a specific signaling-to-expression axis. This requires precise genetic models that can knockout, mutate, tag, or overexpress the gene of interest in relevant cell types. EDITGENE provides end-to-end CRISPR services to generate such models, enabling rigorous testing of hypotheses and acceleration of therapeutic discovery.
Contact EDITGENE today to design your custom CRISPR model for signal transduction involved in regulation of gene expression research.
Frequently Asked Questions About signal transduction involved in regulation of gene expression
What is GO:0023019?
GO:0023019 is a Gene Ontology biological process term defined as any process that modulates the frequency, rate or extent of gene expression as a consequence of a process in which a signal is released and/or conveyed from one location to another.
What genes are involved in signal transduction involved in regulation of gene expression?
Key genes include ESR1, ESR2, CTNNB1, APC, NFE2L2, KEAP1, HMOX1, ChREBP, SREBP, and members of the GRAS family in plants, among others [1, 3, 4, 7, 8].
How does estrogen receptor signaling regulate gene expression?
Estrogen binds to ESR1, causing receptor dimerization and nuclear translocation, where it binds estrogen response elements and recruits coactivators to activate target gene transcription.
What is the role of Wnt/beta-catenin signaling in gene expression?
Wnt ligands stabilize beta-catenin, which enters the nucleus and partners with TCF/LEF transcription factors to activate developmental and oncogenic gene programs.
How is Nrf2 signaling linked to gene expression?
Oxidative stress inhibits KEAP1-mediated degradation of NFE2L2 (Nrf2), allowing it to accumulate and induce antioxidant genes such as HMOX1.
What diseases are associated with dysregulated signal transduction to gene expression?
Cancer, metabolic disorders, inflammatory diseases, and neurological channelopathies are linked to defects in these pathways [1, 3, 4, 6, 7].
How can CRISPR be used to study GO:0023019?
CRISPR knockout, point mutation, knock-in, and overexpression models allow researchers to perturb signaling genes and measure downstream gene expression changes, establishing causality.
What methods are used to study signal transduction involved in regulation of gene expression?
Common methods include RNA-seq, ChIP-seq, ATAC-seq, proteomics, phosphoproteomics, reporter assays, and live-cell imaging [1, 2, 3, 4].
What is the synonym for GO:0023019?
The synonym is 'regulation of gene expression as a consequence of signal transmission'.
Why is GO:0023019 important for drug discovery?
It identifies signaling nodes that control disease-associated gene expression, offering targets for therapeutic intervention in cancer, metabolic, and inflammatory diseases [1, 3, 4].
Conclusion
GO:0023019, signal transduction involved in regulation of gene expression, represents a fundamental biological process that connects extracellular and intracellular signals to changes in gene expression. Its components, including hormone receptors, Wnt pathway effectors, and oxidative stress sensors, are critical for normal physiology and are frequently dysregulated in disease [1, 3, 4, 7]. Understanding this process requires integrated experimental approaches, from CRISPR-based genetic models to multi-omics profiling. EDITGENE provides comprehensive services to support research on this term, enabling precise manipulation and analysis of signaling-to-expression networks.
References
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- 2. Jaenisch R et al.. 2003. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals.. Nat Genet 33 Suppl:245-54 PMID: 12610534
- 3. Clevers H. 2006. Wnt/beta-catenin signaling in development and disease.. Cell 127(3):469-80 PMID: 17081971
- 4. Medina MV et al.. 2020. Regulation of the Expression of Heme Oxygenase-1: Signal Transduction, Gene Promoter Activation, and Beyond.. Antioxid Redox Signal 32(14):1033-1044 PMID: 31861960
- 5. Oh Y et al.. 2023. Mycobacterial Regulatory Systems Involved in the Regulation of Gene Expression Under Respiration-Inhibitory Conditions.. J Microbiol 61(3):297-315 PMID: 36847970
- 6. Sashihara S et al.. 1998. Oncogenes and signal transduction pathways involved in the regulation of Na+ channel expression.. Crit Rev Oncog 9(1):19-34 PMID: 9754445
- 7. Foufelle F et al.. 1998. Glucose regulation of gene expression.. Curr Opin Clin Nutr Metab Care 1(4):323-8 PMID: 10565368
- 8. Khan Y et al.. 2022. Expression and roles of GRAS gene family in plant growth, signal transduction, biotic and abiotic stress resistance and symbiosis formation-a review.. Plant Biol (Stuttg) 24(3):404-416 PMID: 34854195
