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.
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