The HAT proteins modify histone tails giving rise to a more open chromatin structure capable of binding the transcription initiation machinery.[35] Recruitment of co-activators is regulated by AR acetylation by proteins such as p300 and Tip60, which is itself upregulated by androgen ablation.[36] It has been suggested that over-expression of co-activators may provide a mechanism for transition to hormone refractory prostate cancer by amplifying the response to adrenal androgens. This evidence concerns the gene AR and prostate carcinoma.