A: INHAT is associated with a GRE-containing promoter at the baseline state, binding histones and protecting them from transcription factor/nuclear receptor coactivator HAT-mediated acetylation. Once ligand becomes available, activated GR induces dissociation of INHAT from histones through physical interaction with Set/TAF-Iβ, making these histones susceptible to HAT-induced acetylation.
B: Pathologic Set-Can fusion protein remains associated with GREs in the presence of glucocorticoids, suppressing GR-induced transcriptional activity by preventing HAT-induced histone acetylation.
INHAT: inhibitor of the histone acetyltransferases, HAT: histone acetyltransferase, GR: glucocorticoid receptor, GREs: glucocorticoid response elements.