In humans, the glucocorticoid receptor gene (GR, alternatively GCR) is encoded for by the NR3C1 gene (also known as GR1F), which spans roughly 80 kb in chromosome five. The NR3C1 gene, which is a protein-coding gene, has two functions: i) it can work as a transcription factor that binds to glucocorticoid response components, or glucocorticoid response elements (GRE)—both for mitochondrial and nuclear DNA—in the promoters of the genes responsive to glucocorticoids, which subsequently activate transcription; ii) it can regulate and modulate other transcription factors. The NR3C1 gene is generally found in the cytoplasm, but in the ligand-binding process, it can move to the cell nucleus.
Mutations in the NR3C1 gene are associated with various mental disorders such as post-traumatic stress disorder, generalized stress disorder, and also glucocorticoid resistance caused by a mutation in the glucocorticoid receptor (GR).
The NR3C1 gene is the homolog of the exon 1(7) region in the rat glucocorticoid receptor, which can be epigenetically modified by maternal behaviors that subsequently impact the pup’s ability to cope with acute stressors.
McGowan, P. et al. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature neuroscience, 12(3), pp.342–348.
Weaver, G. et.al. (2004). Epigenetic programming by maternal behavior. Nature neuroscience, 7(8), pp.847–854.