Abstract
In recent years, it has been established that environmental stress leaves enduring traces at distinct sites on the chromatin, accompanied by permanent alterations of gene transcription. This process depends on duration and extent of the discharge of stress hormones. Here, we aimed at identifying genes that are both regulated by the glucocorticoid receptor (GR) and display epigenetic features of transcriptional control. We used neuronal Neuro-2a cells as model system; cells were transiently transfected with GR and exposed to dexamethasone (Dex) for 2 days, either under conditions of cell proliferation or after serum deprivation-induced growth arrest. In parallel, Neuro-2a cells were treated with the histone deacetylase inhibitor trichostatin A. Comparison of gene expression profiles obtained from wholegenome microarray analyses revealed a network of genes that were GR-dependent and under control of epigenetic factors. Gene set enrichment analysis was performed in order to obtain insight into functional mechanisms implicated in stress hormone physiology. Dex response varied between proliferating and growth-arrested cells; enrichment was found for genes associated with metabolic pathways in proliferating cells, and for genes linked to inflammation in growth-arrested cells. The set of genes that were regulated by Dex under both growth conditions (proliferation and arrest) as well as by trichostatin A - (under cell proliferation) was enriched in mRNA transcripts encoding proteins which play a role in development and homeostasis. In summary, this study introduces a conceptual approach and incipient proof-of-concept for the identification of candidate genes that might be epigenetically programmed by activated GR.
Keywords: Dexamethasone, gene set enrichment analysis, glucocorticoid receptor, histone, microarray.
CNS & Neurological Disorders - Drug Targets
Title:Comparison of Glucocorticoid Receptor- and Epigenetically Regulated Genes in Proliferating Versus Growth-Arrested Neuro-2a Cells
Volume: 12 Issue: 8
Author(s): Jurgen Zschocke, Peter Weber, Nicole Zimmermann and Theo Rein
Affiliation:
Keywords: Dexamethasone, gene set enrichment analysis, glucocorticoid receptor, histone, microarray.
Abstract: In recent years, it has been established that environmental stress leaves enduring traces at distinct sites on the chromatin, accompanied by permanent alterations of gene transcription. This process depends on duration and extent of the discharge of stress hormones. Here, we aimed at identifying genes that are both regulated by the glucocorticoid receptor (GR) and display epigenetic features of transcriptional control. We used neuronal Neuro-2a cells as model system; cells were transiently transfected with GR and exposed to dexamethasone (Dex) for 2 days, either under conditions of cell proliferation or after serum deprivation-induced growth arrest. In parallel, Neuro-2a cells were treated with the histone deacetylase inhibitor trichostatin A. Comparison of gene expression profiles obtained from wholegenome microarray analyses revealed a network of genes that were GR-dependent and under control of epigenetic factors. Gene set enrichment analysis was performed in order to obtain insight into functional mechanisms implicated in stress hormone physiology. Dex response varied between proliferating and growth-arrested cells; enrichment was found for genes associated with metabolic pathways in proliferating cells, and for genes linked to inflammation in growth-arrested cells. The set of genes that were regulated by Dex under both growth conditions (proliferation and arrest) as well as by trichostatin A - (under cell proliferation) was enriched in mRNA transcripts encoding proteins which play a role in development and homeostasis. In summary, this study introduces a conceptual approach and incipient proof-of-concept for the identification of candidate genes that might be epigenetically programmed by activated GR.
Export Options
About this article
Cite this article as:
Zschocke Jurgen, Weber Peter, Zimmermann Nicole and Rein Theo, Comparison of Glucocorticoid Receptor- and Epigenetically Regulated Genes in Proliferating Versus Growth-Arrested Neuro-2a Cells, CNS & Neurological Disorders - Drug Targets 2013; 12 (8) . https://dx.doi.org/10.2174/187152731131200126
DOI https://dx.doi.org/10.2174/187152731131200126 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Molecular Mechanisms of Neuronal Histamine and its Receptors in Obesity
Current Molecular Pharmacology Fibroblast Growth Factors, Fibroblast Growth Factor Receptors, Diseases, and Drugs
Recent Patents on Cardiovascular Drug Discovery Resveratrol and Cancer: Chemoprevention, Apoptosis, and Chemoimmunosensitizing Activities
Current Medicinal Chemistry - Anti-Cancer Agents Alzheimer Disease: What Role for Leptin and Insulin?
Central Nervous System Agents in Medicinal Chemistry The Medicinal Chemistry of Peptides
Current Medicinal Chemistry The Role of NF-κB Inhibitors in Cell Response to Radiation
Current Medicinal Chemistry The Development of Copper Radiopharmaceuticals for Imaging and Therapy
Medicinal Chemistry Molecular Imaging of Therapeutic Potential of Reporter Probes
Current Drug Targets Interaction of Prolyl Oligopeptidase with α-Synuclein
CNS & Neurological Disorders - Drug Targets Emerging Therapies Targeting Tumor Vasculature in Multiple Myeloma and other Hematologic and Solid Malignancies
Current Cancer Drug Targets Proteasome Structure, Function, and Lessons Learned from Beta-Lactone Inhibitors
Current Topics in Medicinal Chemistry Cytokines and Chemokines as Regulators of Angiogenesis in Health and Disease
Current Pharmaceutical Design Inhibitory Activity of Curcumin Derivatives Towards Metal-Free and Metal-Induced Amyloid-β Aggregation
Current Alzheimer Research TRP Channels: New Potential Therapeutic Approaches in CNS Neuropathies
CNS & Neurological Disorders - Drug Targets Functionalized Carbon Nano-scale Drug Delivery Systems From Biowaste Sago Bark For Cancer Cell Imaging
Current Drug Delivery Biological Activity and Delivery of Peptide Nucleic Acids (PNA)-DNA Chimeras for Transcription Factor Decoy (TFD) Pharmacotherapy
Current Medicinal Chemistry MicroRNA Polymorphisms, MicroRNA Pharmacogenomics and Cancer Susceptibility
Current Pharmacogenomics and Personalized Medicine Effect of DNA Repair Deficiencies on the Cytotoxicity of Drugs Used in Cancer Therapy - A Review
Current Medicinal Chemistry SYNTHESIS AND APPLICATIONS OF Fe3O4/SiO2 CORE-SHELL MATERIALS
Current Pharmaceutical Design Autophagy Enhancer Carbamazepine Alleviates Memory Deficits and Cerebral Amyloid-β Pathology in a Mouse Model of Alzheimer's Disease
Current Alzheimer Research