FIG. 9.
Model showing crosstalk between ERα and AhR and the key role of the coregulator RIP140 as a corepressor or coactivator in gene regulation in breast cancer cells. (A) In cells containing ERα and AhR, treatment with E2 results in the formation of a multimeric chromatin complex containing liganded ERα, unliganded AhR, ARNT, and RIP140. In this situation, AhR and RIP140 act as corepressors of E2-ERα gene expression. (B) In cells exposed to dioxin only, and not E2, at gene sites containing EREs and DREs, liganded AhR recruits RIP140 to the unliganded ERα, AhR-ARNT complex, and RIP140 acts as a corepressor of dioxin-AhR gene expression. However, at genes such as CYP1A1, which has only DREs, RIP140 acts as a coactivator of gene expression. Hence, in panel A, the presence of AhR fine-tunes and dampens the magnitude of gene stimulation by E2-ERα. In panel B (left), dioxin-AhR gene activity is modulated by ERα and RIP140 presence at genes with both ERE- and DRE-binding sites. At sites with DREs only (panel B, right), in the absence of ERα chromatin binding, RIP140 acts as a coactivator of gene regulation. Thus, the presence or absence of ERα at a gene regulatory site appears to be the determinant of whether RIP140 functions as a corepressor or coactivator.