Figure 7

Schematic figure of cortisol-induced ZBTB16 as part of intracellular feedback regulation of GR signaling. Baseline 1: Under low cortisol baseline condition, there is low basal GR transcriptional activity. Induction 2: Under stimulated (high cortisol) conditions, GR induces target genes via transactivation, including ZBTB16, and represses other GR target genes. Adaptation 3: Cortisol-induced ZBTB16 protein modulates GR-mediated transcriptional activities by potentiating transrepression and attenuating transactivation effects in a gene-specific manner. This orchestrated activity of glucocorticoid-induced ZBTB16 restores the cellular condition to its baseline state and therefore may be part of an intracellular negative feedback loop. Thick arrows indicate increased transcriptional activity, thin arrows indicate normal or reduced transcriptional activity, and the dashed arrows in gray indicate potential mechanisms. GR: glucocorticoid receptor, GRE: glucocorticoid response elements, nGRE: negative glucocorticoid response elements, NF-κB RE: NF-κB response elements, TFs: transcription factors. Created in BioRender. Galuh, S. (2025) https://BioRender.com/i82d546.