FIG. 9.

Coordinated sequential recruitment of HDACs, G9a, and Swi/Snf-Brm in the SHP-mediated suppression of CYP7A1 in the hepatic bile acid metabolism. Bile acid-induced SHP may compete with coactivator HATs, including p300, CBP, and SRC-1, at the CYP7A1 promoter, which contributes to a decrease in histone acetylation initially as proposed before. SHP directly interacts with HDACs and G9a through its C and N terminus, respectively, recruiting these cofactors to the promoter, which results in deacetylation and subsequent dimethylation at the H3K9. H3K9 methylation and deacetylation create a binding surface for the recruitment of the Swi/Snf-Brm complex, which results in ATP-dependent chromatin remodeling and subsequent gene silencing of CYP7A1.