Bioinformatics Analyses of Spatial Peripheral Circadian Clock-Mediated Gene Expression of Glucocorticoid Receptor-Related Genes.

Glucocorticoids are ubiquitous, pleotropic steroid hormones secreted from the cortices of the adrenal glands in a circadian fashion under the strong influence of the central Clock center located in the suprachiasmatic nuclei (SCN) of the hypothalamus. In previous work, we reported that the circadian transcription factor CLOCK and its heterodimer partner BMAL1 suppress the transcriptional activity of the glucocorticoid receptor (GR) by acetylating a lysine cluster located in its hinge region between the DNA- and ligand-binding domains. This regulation of GR transcriptional activity by CLOCK/BMAL1 functions as a counter-regulatory loop against the diurnally fluctuating circulating glucocorticoids. Here, we have performed further analyses of our data using bioinformatics and computational methods. Gene expression data were analyzed using unsupervised machine learning methods, such as hierarchical clustering, k-means, Naïve Bayes classification, and polynomial regression analyses. We determined expression patterns of Clock-related genes, unraveled the dynamics of spatial data, and defined the temporal function of Clock-mediated GR-regulated genes. Gene expressions manifested nonlinear dynamics, possibly because we obtained dynamic results from stationary measurements. The mechanics of the circadian rhythms are still obscure, and more studies are required to understand how such rhythms influence mammalian physiology.