N-terminal sequences of the human androgen receptor in DNA binding and transrepressing functions.

Androgen receptor is a ligand binding transcription factor that controls several physiological processes ranging from the development of the male sexual organs to the acquisition of secondary sex characteristics. It is composed of a carboxy-terminal ligand binding domain, a centrally located DNA binding domain and an amino terminal modulator region. Detailed study on the DNA and carboxy-terminal regions have been carried out, but only limited information is available on the activity of the N-terminus. With the use of truncated and chimeric receptor constructs we have demonstrated in transient transfection experiments that the N-terminus of the androgen receptor contributes to DNA binding, transactivation and transrepression functions of the receptor. We have shown that specific sequences at the N-terminus are needed for transactivation but we were unable to identify discrete sequences in this region for the DNA binding and transrepression functions. Sequences from the transcription factor NFI/X3 that bear no homology to the N-terminus of the androgen receptor nevertheless functionally replaced it in enhancing DNA binding, transrepression but not transactivation functions of the receptor. Thus, it appears that the structure rather than sequence specific elements determines the contribution of the N-terminus of the androgen receptor to DNA binding and transrepression functions.