transrepression

Transrepression is a mode of transcriptional regulation in which a regulator represses the expression of genes other than those from which it is encoded, acting in trans. In many cases, transrepression does not involve direct binding of the regulator to the target gene’s promoter. Instead, the regulator influences the activity of other transcription factors or the transcriptional machinery, reducing transcription from their target genes.

Mechanisms commonly involved include protein–protein interactions that tether a regulator to DNA-bound activators, recruitment of corepressors and chromatin-modifying enzymes (such as histone deacetylases) to shared target loci, sequestration or “squelching” of coactivators, and chromatin remodeling that makes promoters less accessible. These interactions can dampen the ability of activators to recruit RNA polymerase II or alter the chromatin environment to a repressive state.

Among well-described examples, the glucocorticoid receptor mediates transrepression of inflammatory genes by interfering with transcription factors like NF-κB and AP-1. This mechanism contributes to the anti-inflammatory effects of corticosteroids. Other nuclear receptors and transcriptional regulators can also exert transrepressive effects under certain conditions, illustrating the broader role of transrepression in cellular signaling networks.

Transrepression is distinct from cis-regulatory mechanisms, where regulatory elements act on nearby genes on the same DNA molecule, and from classic transcriptional activation. It is context-dependent, influenced by ligand binding, cellular state, and the repertoire of interacting proteins, and it has implications for physiology and therapeutics in inflammation, cancer, and beyond.