Direct, androgen receptor-mediated regulation of the FKBP5 gene via a distal enhancer element.

摘要: Androgen signaling via the androgen receptor (AR) transcription factor is crucial to normal prostate homeostasis and tumorigenesis. Current models of AR function are predominantly based on studies prostate-specific antigen regulation in androgen-responsive cell lines. To expand these vitro paradigms, we used mouse elucidate mechanisms through which regulates another direct target, FKBP5, vivo. FKBP5 encodes an immunophilin that has been previously implicated glucocorticoid progestin pathways likely influences physiology presence androgens. In this work, show androgens directly regulate interaction between a distal enhancer located 65 kb downstream start site fifth intron gene. We have found selectively recruits cAMP response element-binding protein enhancer. These interactions, turn, result chromatin remodeling affects proper but not locus as whole. Furthermore, contrast antigen-regulatory mechanisms, transactivation gene does rely single looping complex mediate communication proximal promoter. Rather, basal apparatus communicate indirectly with one another, implicating regulatory mechanism appreciated for target genes.