FHL2, a novel tissue-specific coactivator of the androgen receptor

The control of target gene expression by nuclear receptors requires the rec ruitment of multiple cofactors, However, the exact mechanisms by which nucl ear receptor-cofactor interactions result in tissue-specific gene regulatio n are unclear Here we characterize a novel tissue-specific coactivator for the androgen receptor (AR), which is identical to a previously reported pro tein FHL2/DRAL with unknown function. In the adult, FHL2 is expressed in th e myocardium of the heart and in the epithelial cells of the prostate, wher e it colocalizes with the AR in the nucleus. FHL2 contains a strong, autono mous transactivation function and binds specifically to the AR in vitro and in vivo. In an agonist- and AF-2-dependent manner FHL2 selectively increas es the transcriptional activity of the AR, but not that of any other nuclea r receptor. In addition, the transcription of the prostate-specific AR targ et gene probasin is coactivated by FHL2, Taken together, our data demonstra te that FHL2 is the first LIM-only coactivator of the AR with a unique tiss ue-specific expression pattern.