FIG. 8.

Action of SHP on negative feedback regulation of CYP7A1 in bile acid signaling. Bile acid-induced SHP interacts with the mSin3A/Swi/Snf-Brm complex in cells and recruits the complex to the endogenous human CYP7A1 promoter (A), which results in chromatin remodeling at the promoter chromatin (B). (A) Bile acid treatment also causes dissociation of the p300/CBP/SRC-1 coactivator HAT complex from the promoter. (B) Recruitment of mSin3A/HDAC-1 and dissociation of HATs lead to histone deacetylation at the promoter. Bile acid-induced chromatin remodeling and histone deacetylation both contribute to transcriptional repression after bile acid treatment. (A) The bile acid-activated JNK or ligand-activated PXR (SXR) pathway may contribute to bile acid-mediated CYP7A1 repression independent of the SHP pathway, but the details of the mechanisms are not known, so they are indicated with dashed lines.