Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes including ESR1 and RARB. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Also activator of OCT4 gene expression. Plays a fundamental role in early embryogenesis and regulates embryonic stem cell proliferation and differentiation. Mediator of retinoic acid-regulated preadipocyte proliferation (By similarity). Homodimer (By similarity). Heterodimer; with NR2C2 which is required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats (By similarity). Interacts with ESR1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Interacts with NRIP1 (via its LXXLL motifs); the interaction provides corepressor activity. Interacts with HDAC3 (via the DNA-binding domain); the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Interacts with HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the interaction is required for sumoylation of NR2C1. Interacts with UBE2I; the interaction is required for sumoylation of NR2C1. Interacts with KAT2B; the interaction acts as a corepressor of gene expression (By similarity). Recruited by HDAC3, after all-trans retinoic acid stimulated MAPK1-mediated Thr-223 phosphorylation, to PML bodies for subsequent sumoylation. Sumoylation requires both PIAS1 and UBE2I. Sumoylation appears to dissociate NR2C1 from the PML nuclear bodies. Enhances the interaction with NRIP1 but inhibits interaction with KAT2B. In proliferating cells, stimulation by all-trans retinoic acid, activation of MAPK1-mediated phosphorylation and recruitment to PML bodies with subsequent sumoylation, suppresses OCT4 expression (By similarity). Phosphorylated on several serine and threonine residues. Phosphorylation on Thr-223, stimulated by all-trans retinoic acid (atRA) mediates PML location and sumoylation in proliferating cells which then modulates its association with effector molecules, KAT2B and NRIP1. Phosphorylation on Ser-582 by PKC is important for protein stability and function as activator of RARB (By similarity). Belongs to the nuclear hormone receptor family. NR2 subfamily.