Androgen receptor-mediated gene repression

Abstract

Androgens have an essential role in inducing the genetic program for masculinization during development. Androgens mediate their effect through the androgen receptor (AR), a ligand-controlled transcription factor and regulator of rapid signaling. Inactivated AR results in complete feminization. Androgens are also essential in later life for reproduction, behavior, muscle development, breast, and prostate growth. In general, androgens inhibit breast and promote prostate growth. In the latter context the AR is a major drug target. On the one hand, many insights have been obtained how the AR mediates gene activation on a molecular level. Gene activation is mediated by a battery of factors including coactivators, chromatin remodeling complex proteins and transcription factors which either directly or indirectly interact with the AR at DNA binding sites. On the other hand, there are important AR target genes that are repressed by androgen-bound AR. However, the underlying molecular mechanisms are poorly understood although genes repressed by AR are key factors involved in cell proliferation and invasion. Here, we summarize molecular mechanisms of AR-mediated gene repression, thereby differentiating between direct and indirect DNA/chromatin recruitment and between genomic and non-genomic effects.