Fig. 7.

Schematic representation of molecular mechanism of phenobarbital triggered induction of CYP2B6 in human primary hepatocytes. At noninduced condition, RORα and p-Ser100 RORα occupied the 2B6-RORE motif while HNF4α occupied the OARE, and none of the tested factors were detected on the PBREM. In response to PB treatment, the dynamics of the protein-DNA and protein-protein interactions on the CYP2B6 promoter were changed as a result of CAR recruitment onto the PBREM. As previously reported (Mutoh et al., 2009, 2013), dephosphorylated CAR was translocated into the nucleus and commenced the PB induction process. Then p-Ser100 RORα facilitated the interaction between the factors on the PBREM, RORE, and OARE, thereby enabling the formation of transcriptionally active chromatin complex.