Corepressor

A corepressor downregulates (or represses) the expression of genes by binding to and activating a repressor transcription factor.

[4] In the absence of corepressors and in the presence of coactivators, transcription factors upregulate gene expression.

[12][13] NCoR and SMRT act as a corepressor complex to regulate transcription by becoming activated once the ligand is bound.

[12][13][14][15] Knockouts of NCoR resulted in embryo death, indicating its importance in erythrocytic, thymic, and neural system development.

[19][20] BCOR works with multiple transcription factors and is known to play vital regulatory roles in embryonic development.

[18][19] Similarly, BCORL1 is a corepressor that regulates cellular processes,[21] and was found to be mutated in ~6% of tested AML patients.

Corepressors present many potential avenues for drugs to target a vast range of diseases.

[31][32] Ursodeoxycholic acid (UDCA), by upregulating the corepressor small heterodimer partner interacting leucine zipper protein (SMILE), inhibits the expression of IL-17, an inflammatory cytokine, and suppresses Th17 cells, both implicated in rheumatoid arthritis.

[33][34] This effect is dose-dependent in humans, and UCDA is thought to be another prospective agent of rheumatoid arthritis therapy.