FIG. 9.

Working model for ASCOM function. Upon ligand binding, nuclear receptors undergo a structural change, which signals the replacement of corepressor complexes by a series of distinct coactivator complexes. Three coactivator complexes that contain the well-defined LXXLL motif-based adaptor molecules (SRC-1, ASC-2, and PBP/TRAP220/DRIP205//TRIP2) are shown schematically. These and other coactivators can be selectively recruited to individual receptors under different promoter contexts and cellular conditions (see the text). The SET domains of HALR/ALR might, either directly or indirectly, be involved with methylating H3-K4 and/or other yet unknown substrates in vivo. DN1 competitively blocks receptors from recruiting ASCOM, but not other LXXLL-based complexes, and thus may specifically inhibit ASCOM-mediated H3-K4 methylation of the promoter region.