Figure 12: Clock/Bmal1 suppresses GR-induced transcriptional activity through acetylation. (a) Clock physically interacts with the ligand-binding domain of the GR through its nuclear receptor-interacting domain and suppresses GR-induced transcriptional activity by acetylating via its intrinsic HAT activity a lysine cluster located in the hinge region of the GR,through which (b) Clock reduces affinity of GR to its cognate DNA GREs.

A: acetylation, Bmal1: brain-muscle-arnt-like protein 1, DBD: DNA-binding domain, GR: glucocorticoid receptor, GRE: glucocorticoid response element, HR: hinge region, K: lysine residue, LBD: ligand-binding domain, NTD: N-terminal domain

C: A heuristic model of the physiologic implications of this study.

From (175).