This accumulation of sterols allows SMO to become active or stay on the membrane for a longer period of time. This hypothesis is supported by the existence of a number of small molecule agonists and antagonists of the pathway that act on SMO. The binding of SHH relieves SMO inhibition, leading to activation of the GLI transcription factors (Process "5"): the activators Gli1 and Gli2 and the repressor Gli3. The sequence of molecular events that connect SMO to GLIs is poorly understood. Activated GLI accumulates in the nucleus (Process "6") and controls the transcription of hedgehog target genes (Process "7"). PTCH1 has recently been reported to repress transcription of hedgehog target genes through a mechanism independent of Smoothened.