RAR-related Orphan Receptor Gamma - Function

Function

The RORγ protein is a DNA-binding transcription factor and is a member of the NR1 subfamily of nuclear receptors. Although the specific functions of this nuclear receptor have not been fully characterized yet, some roles emerge from the literature on the mouse gene.

The RORγ isoform appears to be involved in the regulation of circadian rhythms. This protein can bind to and activate the promoter of the ARNTL (BMAL1) gene, a transcription factor central to the generation of physiological circadian rhythms. Also, since the levels of RORγ are rhythmic in some tissues (liver, kidney), it has been proposed to impose a circadian pattern of expression on a number of clock-controlled genes, for example the cell cycle regulator p21.

RORγt is the more studied of the two isoforms. Its best understood functionality is in the immune system. The transcription factor is essential for lymphoid organogenesis, in particular lymph nodes and Peyer's patches, but not the spleen. RORγt also plays an important regulatory role in thymopoiesis, by reducing apoptosis of thymocytes and promoting thymocyte differentiation into pro-inflammatory T helper 17 (Th17) cells. It also plays a role in inhibiting apoptosis of undifferentiated T cells and promoting their differentiation into Th17 cells, possibly by down regulating the expression of Fas ligand and IL2, respectively .