Figure 1. The signaling events involving geminin, RA signaling and pluripotency factors. RA modulates Wnt signaling (shown in black). Once inside the nucleus, it inhibits Nanog, Oct4, geminin (Gmnn) and Hox gene expression (shown in red), however, whether it mediates these effects through RAR is not known. In turn, RAR modulates Hox and c-myc expression (shown in white) and physically interacts with Brg1 and Smarcd3, while it may bind to the Oct4 and Gmnn genomic loci (shown in green). RAR and Brm are postulated to induce chromatin remodeling and inhibit Nanog and Oct4 expression, upon RA induction, while RAR also modulates Hox gene expression, possibly in co-operation with Brg1. Gmnn regulates Hox expression (shown in white), interacts with Hox and Brg1 proteins and shares bidirectional inhibition with the Wnt signaling pathway (shown in red). HNF4 is predicted to bind to Oct4 and Gmnn sequences (shown in green), while COUP-TF is known to inhibit Oct4 (shown in red) and is predicted to bind to Gmnn (shown in green). Oct4 inhibits COUP-TFII (shown in red) and induces expression of mir-302 (shown in blue), which in turn, inhibits COUPT-TFII (shown in red).